Entropy Production

The Amazing Amnesia of Wall Street

2011-10-27T15:49:00.000-06:00

"Why the European debt deal could kill the CDS market," www.globeandmail.com:

But the economic risk is that hedge funds and other investors give up on the CDS market. Not all money mangers treat the CDS market like a casino. Many purchase insurance on their investments to reduce the risk on their balance sheets. As Mr. Tananbaum pointed out at the Economist magazine’s Buttonwood conference in New York on Thursday, that could result in less investing and by extension, less growth.

“If you can’t hedge your position, you shrink your position,” Mr. Tananbaum said.

Ergh.

Maybe you should be reducing your position, rather than relying on insurance as 100 % of your risk management strategy?

Thank you for Banking

2011-10-25T18:33:00.000-06:00

I have been watching the Occupy Wall Street (OWS) movement with a mix of resignation and admiration. It is nice to see that people are finally starting to get ticked off with the government and corporations that caused a lot of unneeded pain, while I sit on the sidelines with my surly slacktivism. On the other hand, many of the participants seem hopelessly naive and misinformed about what actually happened, and what might be done to fix our society. And really guys, the finger wiggling stuff, it's ridockulous: just stop it. Since this blog is my personal soap-box, I figure it is well past the point to document what I saw happening back in 2008, and where I think the problem lies. Politics ain't my forte, but sometimes a man has to vent.

OWS on the left blames the corporations; the Tea Party on the right blames the government, but neither have accuracy pinpointed the problem. The real problem is the incestuous relationship between corporations and government, and how they've bypassed a lot of the mechanisms (checks and balances) that are supposed to make representative democracy fair. So the protesters, in my opinion, are off-base in protesting the banks. They should be addressing the base of the problem, and occupying K-street in Washington, DC, where many lobbyists are based.

I am reminded of the character Nick Nailor in the movie, "Thank You for Smoking." Nailor is the top-dog of the smoking lobby, and his job is to obscure, confuse, and otherwise muddy the waters so that the tobacco companies can continue to do business as usual, without any pesky facts to confuse consumers (or citizens as some of us old-school folks call people). If you haven't seen it, it's a very smart and clever comedy, and one of my favourite films. At the end of the day, I think the point of the film is the glamourize a scumbag. I.e. the film is lobbying you to admire Nick Nailor, and it is a test to see if you loathe him or not at the end of the movie.

http://www.youtube.com/watch?v=iBELC_vxqhI

However, before I get into the troubles lobbying is wrecking on democracy, let's go back and take a look at what caused the housing crisis. In the most simplistic sense, people were greedy.

The Housing Bubble

The recent real-estate financial crisis was essentially caused by a failure in risk management, which eventually led to the downfall of many financial corporations, but principally Lehman Brothers and AIG. A whole bunch of home loans were made by many actors to people who didn't have the ability to pay down the principle on the properties they were purchasing. This ran the gamete from 'Sub-prime', to the less risky but actually larger magnitude problem hunk of 'Alt-A' loans, and of course craziness like the NINJA (no-income,no-job,no-assets) loans.

The reason all these questionable loans were made was because the companies making the loans were not holding them in order to make money from the interest. Rather, they were packaging them into securities, called collateralized debt obligations (CDOs), to be sold like bonds to ~~suckers~~ interested customers. Now, no one wants to buy a package of NINJA loans, so each securities was divided into pieces called tranches. The bottom tranche took losses, first, then the next level, and so on, until you got to the best tranche, which only lost value if the entire equity was lost. Those top tranches often had AAA and AA ratings, but as it happens, if the housing market declines by 30 %, you in fact do lose every cent of the equity in a mortgage security and even the supposedly AAA tranches got hosed. The housing bubble was not sustainable in the long-term, to the surprise of only people who were not paying attention.

The key problem with traching things this way is how much equity is leveraged up. Unlike you or me, banks are allowed to lend out typically more than 10 x the amount of reserves they hold. In the high of the housing bubble, this reached 30:1 in many cases, which implies if the overall investment declines by only 3.3 %, the whole starting equity is wiped out. In this case, it's easy to see why the AAA tranches were worthless: the housing market declined by an order of magnitude more than the equity could cover.

That wasn't the worst part, however. The worst part was how risk management for those low-hanging tranches that no one wanted was handled. Risk management is generally composed of five different aspects:

Retention
Reduction
Avoidance
Transference through Insurance
Transference through Participant Assumption

Retention is simply acceptance of risk; this is actually how we deal with the majority of risk. Reduction and avoidance are obvious, although in this case reduction (by not loaning money to people who are unlikely to pay it back) and avoidance ("too big to fail") were not really respected. Assumption of risk is things like waivers, it assumes that the participants are informed of what's happening and the people in charge aren't committing fraud (::cough:: ::cough::).

For the housing bubble and mortgage securities,insurance was the risk management tool of choice. In this particular case, they used instruments known as Credit Default Swaps (CDSs). Basically, they're contracts that say if someone defaults on our debt, you pay for it. One can argue back and forth as to whether securitizing mortgages is a problem or not, since if the originator of the mortgage doesn't hold onto it, they lack incentive to ensure the lendee pays it back. However, the financial fobbles came mostly from the idiocy of the tranching at super-high leverage ratios and the cargo cult of finance that insurance through CDSs constitutes sufficient risk management.

The reality is that, for the most part, insurance and assumption of risk don't actually prevent bad things from happening. However, everyone in the financial industry was assuming that their insurance would protect them, not realizing that they were all insuring each other. Insurance only works when the many repay the few that suffer loss. When everyone's a loser, everyone's still a loser even if they're insured. Or in this case, AIG was the bag-holder for too many of the default contracts, and couldn't pay them, so the taxpayers had to do it instead.

Corporations as Artificial Persons

In economics, an externality (or transaction spillover) is a cost or benefit, not transmitted through prices,^[1] incurred by a party who did not agree to the action causing the cost or benefit. A benefit in this case is called a positive externality or external benefit, while a cost is called a negative externality or external cost.

In these cases in a competitive market, prices do not reflect the full costs or benefits of producing or consuming a product or service. Producers and consumers may either not bear all of the costs or not reap all of the benefits of the economic activity, and too much or too little of the good will be produced or consumed in terms of overall costs and benefits to society. [...] (http://en.wikipedia.org/wiki/Externalities).

Corporations have many legal rights, in many cases equivalent to a citizen (see legal personality for some background). This is essentially a requirement for corporations to operate within the legal system. However, there's an accountability problem with how corporations currently legally operate. If a corporation is responsible for negligent manslaughter, does the corporation go to jail?

I think the problem isn't with government or corporations or other large groups of people per sae, but more so a conflict between ethics and morals. We are pretty cooperative, altruistic, and egalitarian animals so a lot of our morals as individuals are hard-wired. A lot of enforcement of this behaviour from the tribe comes from shaming and guilt, but our society has become so huge than individuals have a lot of anonymity. So when a government or corporation does something we would find objectionable from an individual stand-point, the bad behaviour can be rationalized by the participants as, "it's the company doing it."

This comes back to the idea of externalities, and in particular negative externalities and moral hazard. The banking industry took on a bunch of risk, risk they thought they fire-walled themselves away from by purchasing credit default swaps. When the housing bubble burst, their risk management policies failed, and the government had to step in because they were, "too big to fail." As a current, egregious example, consider this: last week, Bank of America was busted for moving derivatives (in the trillions) from an uninsured investment subsidary into a taxpayer insured, deposit subsidy (Bloomberg News). Derivatives aren't real money per sae, but this does show exactly how risk is being off-loaded from financial corporations onto the rest of the world.

Where were the consequences to the individuals working in the FIRE industry burning down the remainder of the (productive) economy? Anyone? So here is where the anger of both the Tea Party and OWS comes from: the financiers have received a multitude of benefits for screwing up, and there was no reciprocation when the collapse occurred. Yes, many middle/upper-class real estate agents and mortgage originators lost their jobs, but most of Wall Street got their bailout money and were left untouched.

The problem, in my opinion, comes from the fact that corporations, as artificial persons, do not vote but have an inordinately large influence onto government because of their ability to hire paid lobbyists. Lobbying is essentially an ethically acceptable form of corruption. I might say that it's analogous to how paraphrasing is an ethically acceptable form plagiarism: we find it vaguely disquieting, but we can't really find enough dirt to call you out on it either. In the end though, lobbying is influence peddling, contains a ton of moral hazard and that makes it wrong.

It's fair and reasonable for other governments (whether they be foreign or domestic) to lobby government officials, and individuals. The problem comes when corporations do it, and in a corrupt fashion. Many lobbyists are former public servants who are then hired to help game the bureaucracy by the corporations they were previously regulating. This is a form of quid pro quo, "do what we want and we'll hire you after you retire," that I think would be considered amoral by most people, but yet it is pretty much the norm, especially in the defence and financial sectors. It is a major disruption of the checks and balances that were originally built into democracies: we need a large bureaucracy to administer our governments, and elected officials are very dependant on the technocrats to execute legislation. So when an international corporation gets its fingers into the pie, we end up with democracy pie with a distinctive oligarchy-filling.

The Race to the Bottom
The last decade has been punctuated by two significant recessions, the dot-com crash and then the housing bubble. Aside from those events, growth has been quite impressive. However, it has also been quite uneven, with a lot of people being left behind.

What is perhaps less obvious is that social dislocation may also follow periods of rapid growth, since the benefits of growth are very seldom evenly distributed. Indeed, it may be precisely the minority of winners in an upswing who are targeted for retribution in a subsequent downswing. (Niall Ferguson, The War of the World, p.lxii)

In the above quote, Ferguson is talking about how Jews benefited from the increasing urbanization of Europe following the great depressions of the 1870s and 1890s, and how this made them a target on the basis of tribalization, following the great depression of the 1930s. It is pretty apropos for our current mess too.

The growth starting after the dot-com crash up to the housing market crash of 2008 was largely a mirage. In a lot of ways, it was a jobless recovery. Productivity increased, wealth increased, but in general many people were left behind. The employment index gives a much fairer impression of the scale of the problem than any unemployment rate ever could.

The proportion of employed persons in the USA (from Calculated Risk). Note the y-axis does not originate at zero.

Roughly 5 % of the jobs in the USA have simply disappeared over the past ten years and is at the same level seen in the 1970s. That means that 1 in 20 people have permanently left the workforce. At that level, everyone will know someone who's no longer working, and badly effected demographics will know many people. I cannot believe that conservative pundits are are not screaming bloody murder about having so many people out of the workforce since all of them have to be supported by the working population.

This brings me to the notion of the race to the bottom. That is, he idea that you need to attract businesses by making regulations that protect the environment, workers, and offering tax breaks and subsidies. This to me sort of says, we think our local industry is incompetent, and we need to bring in a multinational to provide jobs rather than build our own economy. I.e. it's lazy governing. The main winners in the deregulation sweepstakes of the finance industry were the USA, Ireland, and Iceland. How well did that work out for you guys? I think the dichotomy that we have to allow bad actor corporations to operate in our boarders to keep people employed is a false one: why cannot the elimination of a naughty corporation allow space for a nice corporation to win market share?

Bad actor corporations are just that, and they tend to be a net-negative on the economy. Just as an example, look at high-frequency trading. What is the economic benefit to high-frequency trading? To my eye, it seems the more ~~sophisticated~~ complicated financial instruments become, the less benefit they provide to the rest of society as legitimate instruments of providing credit to the rest of the economy. The Keep It Simple, Stupid (KISS) should rule our laws surrounding finance.

Try to think of capitalism as a sandbox experiment in evolution. The initial conditions and rules that govern our little experiment will determine what sort of corporate mileau that pops out the other end. If we have rules that allows negative externalities to be produced without any negative consequences, of course the end result will favour the corporate animals that produce a lot of them. If we want to get more altruistic companies in our countries, we need to make sure the sandbox favours them. If you want more Enrons, deregulate and race to the bottom.

First, the USA has to figure out what direction it wants to take its economy in because too many people have been left without a livelihood. Exporting imperialism, sustainability, high-tech manufacturing, whatever... Right now 20 - 25 % of the US economy is in the FIRE (financial, insurance, and real estate) sector and sorry but that's silly. You cannot produce wealth by shuffling around pieces of paper (or more likely, bits in computer memory). The FIRE sector is essential, but also essentially parasitic on the rest of the economy. It's the only sector that has become more bloated and less efficient with the massive gains in information technology over the past half-century, and that indicates to me that something is wrong with the laws and regulations that govern it.

We need to recognize that there's a need for a balanced economy, because honestly you cannot have everyone doing research and development, developing new ideas and products. I'm barely smart enough to do research myself, in my own tiny little highly specialized field. Germany does it; Japan does it.

Second, occupy K-street. Wall Street seems to be doing too good of a job of populating the US Treasury Department and Financial Reserve with their own people. Laws and regulations are not a bad thing, but there is a tendency due to excessive political partisanship for these to not be flexible, living rules. I think it is fair to say that in the USA, the blame for excessive partisanship should largely lie on the GOP and their righteous, doctrinaire approach to governance. Regardless, the rules surrounding political lobbying and the various forms of, well, bribery that are allowed to go on need to be tightened up immensely.

Third, the Euro needs to go. I haven't talked about the Eurozone at all, but I think it's fair to say, sovereign governments not being in charge of their own currency has caused 'issues.' It was a technocratic solution imposed from the top without a plurality of support.

I wouldn't want to come across as histrionic, the system actually works pretty well, but it does need to be reformed to deal with the reality of international corporations being artificial persons with little to no accountability to anyone. Most people in the West are fabulously wealthy by any historical standard, and technology continues to march on, but clearly things could be better as change has outstripped some of the rules our culture lives by. Corruption is never a positive thing and we should always try to stamp it out whenever we can.So no violent revolution please, just real reforms, and end the race to the bottom, because we don't want to be at the bottom.

Fusion Power, Steampunk-style

2011-10-18T17:46:00.001-06:00

Harnessing the power of fusing hydrogen isotopes together has long been a staple of science fiction, a means of achieving otherwise unachievable power densities, so as to make so many gee-whiz devices within the realm of the possible. In reality, fusion design concepts are generally massive, cantankerous, and incredibly expensive (see magnetic confinement fusion and internal confinement fusion). Fusion has been practical for awhile now, but it generally requires more energy input than it outputs, and the prototypes have been ludicrously expensive. The joke is with fusion, with research that's been ongoing for fifty years, is that it's always and always will be, "twenty years away."

In order to make hydrogen fuse, the first step is to get it hot enough that it ionizes, such that the electrons are no longer attached to a nucleus, forming the forth-form of matter, a plasma. Generally, the aim is to bring together a Deuterium (proton+neutron) ion and a Tritium (proton+2 neutrons) ion close enough together that the strong nuclear force affects the fusion of the two ions. However, the electrostatic charge on the ions is a longer range force, and it tends to mess up collision trajectories, such that only very high energy ions on a direct collision course could ever fuse. So the temperatures required are quite massive.

The magnetic confinement tokamak design that most people will be familiar with due to its widespread coverage in popular science magazines, tries to achieve more or less steady-state fusion power. Steady-state fusion tends to be plagued by energy losses, particularly turbulence in the plasma, that bleeds off power. In comparison, pulsed concepts like internal confinement are easier to initiate, but the natural tendency of an extremely hot gas is to expand rapidly, so fusion rapidly slows and stops, limiting the overall efficiency of the process.

Ok, enough background: enter General Fusion, a company based in British Columbia, that is angling to build a fusion power generator that, well, seems like it would fit right into a Steampunk science fiction novel! It's the one fusion concept that I've seen that one could conceivable build using relatively low-technology components: pistons, microwave ovens, that sort of thing. It's something MacGyver might build.

Magnetized Target Fusion (MTF) is a hybrid concept that is supposed to be low-cost. It was first proposed in 1976 as the LINUS concept, and it relies on first forming a small ball of deuterium and tritium plasma, called a plasmoid (or sometimes a spheromak). The plasmoid is given some angular momentum, such that it's actually a vortex, so that it has an inherent magnetic field that holds the plasmoid together for a brief moment. The plasmoid, which is already pretty warm, is then compressed so that a pulse of fusion occurs.

The main advantage of forming a plasmoid first, over the plain inertial design, is efficiency in transferring energy from electricity into the plasma. Lasers, plain and simple, aren't efficient at converting electricity to coherent light — I don't know what the lasing efficiency is at the National Ignition Facility, but commercial solid-state lasers are usually in the single digits. In comparison, a plasmoid can be formed with basically a high-tech microwave, using radio-frequency radiation, and the conversion efficiency is very very high.

Of course, the next question is, how to compress the plasmoid? A plasmoid has a lifetime of approximately 100 μs according to General Fusion, so compression has to occur on that timescale. The proposed solution is to use over two-hundred pistons driven by compressed air to smash into the 'pot' holding the plasmoid, inducing a converging acoustical wave. As the wave converges, its strength increases and it collapses the plasmoid to very high pressures, ~1 Megabar and results in a enormously high magnetic field within the collapsed plasmoid, on the order of 1000 Telsa. Effectively, it's like an artificial implosion nuclear bomb, using a very small amount of material. By using pneumatically-driven pistons instead of say, lasers, to achieve compression General Fusion is again gaining major efficiencies in terms of their energy input to output ratio (aka 'gain' in the fusion world). Air can be compressed relatively efficiently up to thermodynamic limits, so the whole concept doesn't have massively lossy steps that crush the overall system efficiency.

Since the pistons are basically flat, the shock wave will actually not be perfectly spherical. Also, it's pratically impossible to get all the pistons to hit the sphere at the exact same time — General Fusion claims they have accurate control of the impact time down to 5 μs which is 'good enough.' Since there will always be some error in the impact timing, the shock wave will imperfectly compress the plasmoid and one can expect a lot of cavitation and other hypervelocity fluid dynamical effects. The cavitation is similar to shaped-charge explosives, in that very high-speed jets are formed. I am not very clear on the physics of these plasma jets, but I would guess that they are basically the source of the ultra-high temperatures that make fusion possible with this concept. So cavitation early in the compression of the plasmoid is bad, because it bleeds off energy and reduces the ultimate compression achieved. However, a certain amount is probably desirable once the pressure reaches its ultimate limit.

Figure 1: General Fusion's pneumatic fusion reactor concept (http://www.generalfusion.com/generator_design.html). Plasmoids are formed in the plasma injectors (cones on the top and bottom) and then injected into the 'pot' of liquid lead and lithium. The two plasmoids collide in the middle and are metastable for a brief instant. The pot is surrounded by 220 pneumatically driven pistons which hammer the side of the pot, creating an imploding acoustical wave that compresses the plasmoid, causing a pulse of nuclear fusion.

The pot itself is actually full of a mixture of liquid lead and lithium metals, as there's a need for an 'aether' to transmit the acoustical energy. The lead acts as a neutron/thermal heat sink, absorbing the energy from neutrons produced by the fusion event both to recover it in the form of heat but also to protect the rest of the machine from high-energy neutron radiation. The lead-lithium mixture carries the heat produced by the fusion pulse to some working fluid (i.e. water) which can then produce electrical power.

The lithium is a slow neutron absorber, but it also undergoes fission to hydrogen and helium isotopes (via n + ⁶Li → T + ⁴He and n + ⁷Li → T + ⁴He + n), thus acting as a source of tritium, which is very expensive, radioactive, has a tendancy to leak through solid materials, and dangerous, since it can be used to make hydrogen bombs. Hence the reactor is designed to have a high breeding ratio (claimed at 1.6:1), so that once a little tritanium is given as a starter, more comes out.

Flowing the lead-liquid mixture in and out of the pot is likely a little tricky because the mixture has to spin in the pot, so as to setup favourable conditions for the plasmoid collision.

For the test-bed unit, which is smaller than an industrial scale reactor would likely be due to efficiencies of scale, about 100 Megajoules of mechanical energy is required as an input and about 600 MJ of thermal energy is produced. The heat can then be used to make steam, just like any other thermal power plant, and recovered at around a 33 % efficiency, so that 200 MJ of electrical energy is produced per shot. Hence the net would be 100 MJ per shot, and the target goal is 1 shot per second, thus producing 100 MW of power.

There are of course a variety of problems with the concept. One of the biggest is getting the two plasmoids to collide and combine in the desired manner to form a little vortex of plasma in the centre of the pot. This is a hard thing to test without two working plasma injectors and a pot of liquid lead-lithium. Currently they are relying on simulations, and there is plans for an explosive-based compression test to see if their plasma injector is working as desired. The disadvantage of the explosive-based method is that it's destructive, so they can only get one test per boom-boom. This makes iterating the design expensive and manpower intensive, but they are planning a shot in the fall of 2012 without Tritium.

Another problem is that material from the pot or the plasma injector nozzles (called spalling in the tokamak field) will be absorbed into the lead-lithium liquid, and that these impurities will radically increase the rate at which the plasmoids dissapate.

Irradiation of the machine itself is also a problem. The lead-lithium matrix will absorb 99.9999 % of the neutrons but the walls of the vessel will still become too radioactive after about six months of use. Fortunately neutron embrittlement should not be a problem because the neutrons should be moving at relatively low velocities by the time they get to the shell of the pot.

Lifetime of the shell and pistons is also a concern, due to the thermal and shock stress caused by the impacts. This is actually something that improves as the machine gets bigger, because the pistons can move slower in order to achieve the same overall compression ratio.

When I describe this concept as being steampunk-themed, I am exaggerating a bit. In fact, this concept requires exquisite timing to control all the pneumatically driven pistons, and to form and inject the plasmoids into the liquid lithium-lead chamber, and that means lots of fibre-optics and other high-speed network devices unavailable 20-30 years ago. It is definitely the hipster of fusion power schemes, however.

The bottom line: I remain skeptical that nuclear fusion can be more economical than either photovoltaics, which will eventually be the cheapest source of power on the planet, or advanced fission reactors. Fusion is one of those gee-whiz things that sounds really exciting, until you start getting into the details and wonder how it will be economical, and the radiation waste aspect isn't really any better than fission (there's no worry about products decaying into Radon, which is a radioactive gas, but they do have to worry about Tritium contamination of the reactor, and it's a gas that can flow in-between the molecules of solid metal). The company has raised about $40 million thus far, and they probably need more than double that to finish their prototype in 2013/14, so it will be interesting to see if they find it. On the other hand, this concept is ripe for science-fiction fodder.

The Corporation (2003) movie

2011-10-13T21:58:00.000-06:00

I recently found out that old but interesting documentary has been released on a 'free' shareware basis

http://www.archive.org/details/The_Corporation_

The Corporation is not an even-handed documentary. It basically lays the claim that the corporate entity, which carries many of the legal rights of a person, has the personality of a psychopath/sociopath.

The basis of this claim is basically two-fold:

The legal definition of a corporation essentially requires it to maximize its growth, its profits, as its primary responsibility to its owners.
Corporations essentially trade on dumping externalizations onto others, i.e. tragedy of the commons.

I don't really agree that corporations are inherently evil, anymore than someone might argue that civil government is inherently evil. Both are organizational constructs that are governed by the laws of the land, and the morals of the people that serve in them. Both can do truly atrocious things, or they can be very beneficial to society as a whole.

I think this documentary is actually pretty topical right now with the 'Occupy Wall Street' movement on the left, and the 'Tea Party' on the right-side of the political spectrum. Both groups object basically to the concentration of power in the hands of unaccountable individuals and institutions. I reference this post on the similarities between the two movements, be sure to check out the Venn diagram:

http://howconservativesdrovemeaway.blogspot.com/2011/10/occupy-wall-street-vs-tea-party.html

Large corporations lobby for the government to have more power, and in return the government enacts laws and regulations favourable to large corporations.

Corporatism isn't capitalism.

Bacon-wrapped Bake Purple Potatoes

2011-04-03T23:59:00.000-06:00

So the other day I decided to make myself brunch, for which I wanted to make something to go with poached eggs. Now, poached eggs boiled in vinegar water four minutes each are a a little runny with the yokes only semi-congealed on the edges, so they need something starchy to sop up the yoke. Hashbrowns could work, but I had some purple potatoes that tend to bleed their pigment, so instead I thought I'd bake them. Then my next brainwave was to wrap them in bacon and chiles, and damn they were tasty.

Ingredients

Two small purple potatoes, half lengthwise
Four strips bacon
(optonal) Pickled green Thai chiles
Salt and pepper, to taste
Olive oil

Slice the potatoes in half, then salt and pepper them. The potatoes were small, not fingerlings but not nearly full-sized baking potatoes. Wrap the bacon around loosely so that the top is well covered. Insert the chiles, and drizzle olive oil on top as 'starter fat' to prevent the bacon from burning. Bake at 350 °F for about 45 minutes, until the potato is cooked through. The bottom of the potatoes should come out nice and golden, and the bacon will shrink wrap around the potatoes. Next time I might microwave the potatoes a bit first to decrease the cooking time and to cook the bacon a little less.

The finished product.

Avalanche Safety Training, Level 1

2011-01-28T11:17:00.000-07:00

So least you readers think I am just being lazy in not posting, here is some photos from an avalanche safety course I took last weekend. We were at Bow Summit for the practical (skiing) portion of the training, here's some pictures sans people.

Sunset the night before.

The skin track up.

The snowpack is about 70 cm of wind-loaded slab on top of 80 cm of very weak sugary surface hoar. The interface is obvious in the picture. In other words very dangerous for slab avalanches. The snowpack was surprisingly strong given how bad it looked (still very dicey over 30°), probably because the top slab was still fairly plastic. We didn't hear any whumpfting (audible evidence of snow settling when skied over).

The view across the valley as the clouds broke up. Ski touring is totally unlike lift-served skiing in tone.

Physical activity should be fun play-time. I don't really get the emphasis on weight lifting in the paleo community, as it seems very boring to me.

M1 and M2 macrophages and the Herpes-virus family

2011-01-04T13:37:00.000-07:00

Ah, the immune system. It is what makes trillion-cell organisms possible. Immune system cells actively patrol the body and attack bacteria, fugii, and parasites. In the process, they often causing collateral damage to self-tissue. The innate immune system compared to the adapted immune system is evolutionarily older and more prone to carpet bombing tactics to defeat pests. As such, when it doesn't operate properly, a broad list of symptoms can present. The innate immune system actually has two roles: both fighting off foreign cells but also repairing damaged tissue. When the innate immune system is always fighting and never repairing it leads to the state of chronic inflammation at the heart of many of the diseases that plague modern civilization, like diabetes, stroke, and heart disease.

What then determines which role an innate immune system cell body operates in at any given time and place in the body? Let's look at monocytes/macrophages.

Monocytes are undifferentiated (i.e. unspecialized) immune system cells of the innate immune system that circulate in the bloodstream. In response to chemical signals from the tissues adjacent to their blood vessels, they enter into the tissue to either fight infection or repair tissue damage. When monocytes enter tissue, their gene expression causes them to become more specialized and they are then called macrophages (they can also become other immune system cells). There are two basic phenotypes for macrophages, which are essentially the ying and yang of the macrophage community.

M1 macrophages are pro-inflammatory and fight infection. They are the classical state for macrophages that you would find described in a textbook. Primarily, they detect and fight foreign organisms (viruses, bacteria, and parasites). They are characterized by the production of pro-inflammatory cytokines, chemicals which alert the other cell types of your immune system to react and destroy the invader (as well as adjacent 'self' cells).
M2 macrophages are anti-inflammatory and repair tissue damage. For example, when you exercise and your muscle tissue is damaged, it is M2 macrophages that infiltrate your muscle organs and affect the repairs [Tidball, 2010] after the initial M1 surge. The characteristic cytokine of M2 macrophages is interleukin-10 (IL-10), which encourages other macrophages to enter the tissue and differentiate into M2 phenotype but also discourage the attention of cyto-toxic 'killer' cells from the lymphocyte family of the immune system.

The differentiation of macrophages, from M1 to M2, is not all that distinct and is generally though to represent the two extremes of a continuum. My reading suggests macrophage populations can make the transition from one phenotype to the other, without die-offs. This is probably a bad thing for chronic modern diseases, in that many of the diseases that are as a result of macrophage dysfunction occur when apoptosis (programmed cell death) is impeded.

One of the beneficial effects of eating a diet low in inflammatory factors (e.g. fructose, wheat, smoking) is that the overall levels of pro-inflammatory hormones, such as cortisol or interferon, are low so the transition from high M1 expression to high M2 expression can occur more rapidly. I strongly suspect this is why most people who transition to the paleo-diet are much better able to put on muscle mass. As the Tidball article indicates, chronic exercise is another no-no because it doesn't give enough time for the M2 macrophages to enter and affect repairs, so the muscle is always in an inflamed state.

This doesn't, in general, appear to actually reduce the ability of the body to fight infectious disease, however. This is probably because even though the overall inflammatory condition (as determined by circulating cortisol globally or cytokines locally) is low, it can easily spike when a foreign body attacks. On the other hand, actual conditions where adrenal functions are suppressed (i.e. Addison's disease), the immune system is hamstrung by the homonal milieu it finds itself in and the immune system doesn't function properly to defend against infection. One hypothetical cause may be that the ratio of M2 to M1 is tilted in favour of M2 in adrenal insufficiency.

One pathogen that is known to mess with the M1/M2 expression in macrophages is human cytomegalovirus (HCMV). HCMV basically takes M2 macrophages or undifferentiated monocytes and reprograms them to be more like M1 macrophages in some ways (Chan et al., 2009 and Chan et al., 2008). Importantly, they do not become like M1 macrophages in that they continue to release interleukin-10, which discourages the adapted immune system from deploying 'killer' lymphocytes (natural-killer cells and T-cells) but encourages more M2 macrophages (red shirts, basically) and at the same time they up-regulate the production of protein filaments that make macrophages motile, so that they can better travel about and infect other organs. So let's all remember, whenever you have massive infiltrate of an organ by macrophages, you can probably bet there's too much IL-10 being produced.

To me the various pathogens that excel at molecular mimicry to hide from the immune system seem to be playing quite the bogey-man role in a whole host of chronic diseases. These are principally the Herpes virus family (which also includes cytomegalovirus and the Epstein-Barr virus which has been linked to chronic fatigue syndrome) and the bacteria C. Pneumoniae, which has been linked to atherosclerosis and a whole host of other chronic diseases. Paul Jaminet over at Perfect Heath Diet has also been covering C. Pneumoniae in the brain,

It also seems a lot of disease symptoms occur when macrophages manifest some combination of the M1 and M2 state. Consider that glucose in the blood is regulated by the liver predominately, so insulin resistance (aka metabolic syndrome) reflects failure of the liver to be able to do it's job. Largely, this is blamed on 'inflammation' in the liver, e.g. alcholic and non-alcoholic fatty liver disease, but what does that mean exactly?

A review (Olefsky and Glass, 2010) states that macrophages in tissue that produce excessive quantities of tumour necrosis factor-α (TNF-α) and interleukin-16 (IL-16) (both pro-inflammatory cytokines), to the point that they are detectable in the blood. I like the following quotation from the review, as it really lays out the problem:

The discovery that adipose tissue from obese mice and humans is infiltrated with increased numbers of macrophages provided a major mechanistic advance into understanding how obesity propagates inflammation (4, 5). Adipose tissue contains bone marrow–derived macrophages, and the content of these macrophages tracks with the degree of obesity (4, 5, 31, 32). In some reports, greater than 40% of the total adipose tissue cell content from obese rodents and humans can be composed of macrophages, compared with ~10% in lean counterparts (32).

That nearly half of fat tissue mass is actually not fat cells, but immune system cells is kind of amazing to me. A very similar thing happens in liver disease. Now, reference #32 is a mouse study (Weisberg et al., 2006) but it in turn cites two other mice studies that are more pertinent (Weisberg et al., 2003 and Xu et al., 2003). Both articles show that gene expression for various proteins that attract immune system cells are strongly up-regulated in the adipose tissue of fat mice. The question is why? Is it diet? I suspect partially, but the revelations regarding what cytomegalovirus can do to macrophages makes me suspect latent pathogens are attracting macrophages as lambs to the slaughter. Are lab mice susceptible to chronic infections given their conditions and short lifespan? Are these latent viruses transmitted from mother to infant?

The prevalence of immune system bodies in the adipose tissue of the obese mice illustrates an example of the, "diseases of civilization," being largely driven by dysfunction of the innate immune system, probably egged on by latent viral and bacterial infections and an unnatural diet. The pieces of the puzzle are mostly there now and evidence will continue to accumulate until we have a better view of the whole picture. Stop the sources of inflammation (i.e. immune system activation), give the immune system the substrates it needs to fight effectively, and the other symptoms will go away.

Inov-8 F-lite 230 Review

2010-11-25T12:53:00.001-07:00

Unfortunately I broke my fibula in March (gymnastics) and did a lot of damage to the various talo-fibula ligaments in the process. Those ligaments are still healing, and one part of my rehab is to do a lot of pseudo-barefoot work, mostly by wearing my Chaco sandles and Vibram KSOs during day-to-day activities. At the very least, I am trying to restore proper biomechanics to my feet, if I have to go through all this discomfort!

However as winter approached I was feeling a little trepidation, since Vibrams are totally unsuited to -20 °C weather conditions with wind and snow. The obvious pick, for me, was to look for some minimalist running flats and stuff some warm socks into them. I'm generally not willing to buy footwear without putting it on first (with the exception of thermo-molded footwear like ski boots), so I headed down to my local eclectic running store, FastTrax, and went through their stock of running flats. Eventually the salesman let me try on the garish blue shoes on the top shelf, the Inov-8 F-lite 230s, which I immediately liked. They are so named for their weight, the shoes as a pair weighs in at 230 grams, or about half a pound. From what I can tell, I'm pretty damn lucky to be able to try these on in a store in Canada as they seem to be hard to find outside of the UK.

'Garish' describes the vivid blue colour quite well

The F-lite 230s is marketed as a 'mountain running flat.' I consider them an ultra-light approach shoe. The lugs on the sole are made of sticky climbing shoe rubber, and they are quite pliable. The heel-lift is probably 3 mm, which makes them pretty much the flattest true shoe I've ever owned. I found them to be immediately comfortable out of the box. The heel box is especially effective in trapping my heel and because the sole is so flexible, there's no noticeable sliding of the heel when walking or running. These shoes are very flexible: it's easy to twist them through 180° or touch the toe to the heel.

The upper is composed of mesh, but the laces are then vertically reinforced by a pliable plastic that helps distribute the forces better so the upper doesn't collapse onto your foot. I think this is a good design decision for light-weight uppers as compared to just a velcro strap.

The most 'non-barefoot style' features of these shoes is: 1.) their general squishiness, and 2.) the pointed, low-volume toe-box.

I find the pointed toe-box a little strange. I probably sized these shoes half-a-size too large as a result; according to the Inov sizing chart I should be wearing size UK6.5 but I actually have size UK7.5s. Realistically, I should probably size for UK7.0. The pointed toe-box does seem to expand out without really putting pressure on my toes, so that's something to consider. I also remember my Vibrams were tight in the right big toe (my right foot is longer than the left) as well and they stretched out.

The shoes also have quite a thick (3 mm) and squishy insole. They can be removed of course, but for now I'm using them. In general if I take the insoles out and just walk around the shoes do not feel nearly as squishy anymore. If I did try to size down into a UK6.5 shoe, I would probably take the insoles out in the store. The finishing of the midsole isn't free of stiching so these shoes probably can't be worn sans insole and sans socks.

The last drawback of these shoes is that the lugs, being composed of climbing rubber, aren't super durable. Inov does have very similar shoes with harder wearing rubber compounds, but I didn't have any choice of models in the store.

It's sort of difficult for me to properly review these things given how I can't really run properly yet, but I have been running in them three times now. Twice was just running to school (about 2 km), which is on pavement. I do not heel strike in these shoes on pavement, even with my limited range of motion in my right ankle. The third time was a trail run at the bottom of the scramble shown in the above picture, and they performed spectacularly well in the soft trail. Foot sensitivity is not as apparent as in the Vibrams, in that small pebbles are unnoticeable but the larger rocks and branches are still felt through the flexible sole just fine, and the lugs make them grip far better in soft ground.

Up on 'Vision Quest' in the David Thompson range.

I have to say, Inov has a very extensive stable of minimalist running shoes designed for natural activities. I find their product line personally pretty compelling (in that I sort of want to buy one of each). If you like hiking and other non-road running activities, go take a look at what they offer on their website. I hope that my local shop brings in some more models, and hopefully I can try a smaller size come summer-time.

Photovoltaics: Multiple Electrons from one Photon

2010-11-16T18:40:00.000-07:00

A month ago a report appeared in Science magazine on a new prototype solar cell that could produce more than one electron, a packet of electrical energy, from one photon, a packet of light energy. This trick isn't new, I discussed a bunch of such concepts years ago in a post on quantum photovoltaics. What's new is that Samber et al. report in "Multiple Exciton Collection in a Sensitized Photovoltaic System," have achieved high efficiency in this process.

The typical goal for these sort of 'quantum' solar projects is to better match the wavelengths of light the photovoltaic system can absorb to that of the spectrum of light that is produced by the sun (and filtered by the atmosphere). The theoretical limit for Silicon alone in a photovoltaic system is 33.7 %, which is known as the Shockley-Quiesser limit. Of course, most commercial PV systems are only around 12 % efficient or less, so there is still considerable room for growth. An example of such a spectrum-matched system is Spectrolab's space photovoltaics, which are actually stacks of multiple photovoltaic systems all operating at different wavelengths, and achieve roughly 30 % efficiency in a commercial product.

Figure 1: The air-mass 1.5 standard spectra (indigo line), which is an estimate for the spectra that arrives at the Earth's surface after passing through the atmosphere. The red line is the band-gap for Silicon; for longer wavelengths (red-er) Si cannot absorb the photon. For shorter (blue-er) wavelengths the extra energy is lost.

If you could get one electron out from a infrared photon and two from a blue photon, then the energy gained is fairly significant. This result has been reported on before, but in this paper, for the first time, the overall system produced more electrons out than photons in, as observed to just isolated nanoparticles. In photovoltaic parlance, the number of electrons produced per photon is known as the quantum yield, but this doesn't describe how many electrons actually escape and result in electrical current. That quantity has the wordy name, absorbed photon-to-current efficiency.

Figure 2: Absorbed photon-to-current efficiency (APCE) as a function of wavelength for the described cells. The x-axis is in electron volts, to convert to wavelength, divide 1240 nm by the photon energy [Fig 4. from Sambur et al., 2010].

Overall,this would be a really interesting paper except for one obvious drawback: the active layer of quantum dots is really really thin. There's only a single layer of quantum dots and given an average diameter of 10 nm, that's not very think for visibile light. Compare that to a standard Silicon cell being hundreds of microns, or a thin-film cell at 10 μm which is still a thousand times thicker. In fact it's so thin that they absorb only 1-2 % of the incoming light.

Since the problem with quantum dot strategies is always getting the electrons out, and not absorbing the light, I'm not sure that this work will have a great impact when scaled up. At the very least, however, it does show that it's possible to build a quantum dot solar cell that works as advertised, producing more than one electron per photon, and doing that quite well.

Schizophrenia and Vitamin D

2010-09-09T17:27:00.000-06:00

A recent short article published in the Archives of General Psychiatry by McGrath et al. (2010) highlights that abnormal vitamin D status in newborn babies is a predictive factor for developing schizophrenia later in life. The study was conducted on 424 patients and 424 controls, all born in Denmark since 1981. Presumably the population the data set was constructed from was very large if they were able to find 424 babies who later developed schziophrenia.

The key finding is that the risk of schziophrenia has a U-shaped curve with neonatal serum concentration, which is illustrated in figure 2 of the article.The findings were statistically significant with a maximum relative risk of 2.1 for having very low vitamin D status compared to the optimum level.

One figure that's sadly lacking from the publication is a histogram of the entire population for vitamin D serum concentration. Since Figure 2 is only given in percentiles, we cannot evaluate what the actual optimal vitamin D concentration is, nor what is too high. I think this is a major oversight in this article.

The potential links between the general family of autism, schizophrenia, and bipolar disorder and vitamin D deficiency have been hypothesized before, such as in this article from the Vitamin D council. Obviously, with a relative risk of 2.0 vitamin D isn't the whole story here, but it likely plays a role in the regulation of brain development. The question is how? Is it a precursor hormone to a development hormone? McGrath referenced an earilier article (on which he was also an author), Eyles et al. (2005) which suggests that vitamin D plays a direct role as a paracrine hormone in the mammalian brain.

Gone Paddling

2010-07-28T21:48:00.000-06:00

So I'm off to Portland, Oregon for a staid conference and a little fun (hopefully) on some of the copious Oregon rivers. Of course on the drive down I'm stopping off in Fernie, BC so I'll have some fun for sure.

I realize the old blog hasn't been getting a lot of attention in the past few months. Basically, I'm busy enjoying my summer and working hard on my Ph.D. program so I really haven't had a lot of spare time on my hands.
I'll be back, it's just that blogging in a purely altruistic activity for me, so something it gets pushed way back on the priority list. If you haven't already done so I would respectfully suggest you use some sort of subscription service, such as Google Reader, to watch my blog.

Meanwhile, some pictures of what I been doing this summer for your enjoyment:

Surfing the Brierlies hole on the North Saskatchewan, near Rocky Mountain House.

A straight-forward little drop on the Castle river, pretty much the only shots I have of me running rapids.

Edging through the rolling waves.

The Mistaya river at low water, at the junction of Jasper and Banff National Park.

The Portage rapid on the Kicking Horse near Golden. The scale is a little deceptive here, those waves are about as tall as a person.

The float before the fun part of the Sunwapta river in Jasper National Park.

I seem to see an absurd number of double rainbows on my travels.

Watching for swimming beginners on the Whirlpool river in Jasper National Park.

Sadly, as things get more difficult in whitewater, the tendency to take pictures drops off, so not too many really fun pictures here. Maybe I should get a helmet camera...

Blog Format Change

2010-05-05T12:07:00.002-06:00

I changed the format of the blog last weekend to allow me to incorporate some widgets more easily. I still have to do a lot of boring HTML work here.

I am having some trouble figuring out how to get the post body and sidebars to fill the screen instead of just the middle third. My old template was so much different in terms of HTML coding. If anyone has a clue how to do this easily within the template XML, please let me know.

Vitamin D Reduces Premature Births

2010-05-05T12:03:00.000-06:00

So on the new front for Vitamin D supplementation it appears that maintaining high levels of vitamin D greatly reduces the risk for premature births (hat-tip to Sharon Kirkey of the Ottawa Citizen). Supplementing with 4000 IU of vitamin D per day compared to 400 IU per day reduces the risk of a premature birth by half. This may have to do with the role of vitamin D in the innate immune system. Previous research published in the New England Journal of Medicine found that around 25-40 % of pre-term events may have been caused by vaginal infections (Goldenburg et al., 2000).

This research isn't published in a peer-reviewed journal yet but rather was presented at the Pediatric Academic Societies meeting in Vancouver, May 1-4. I did, however, manage to track down the abstracts for the conference:

[1665.6] Vitamin D Supplementation during Pregnancy Part 2 NICHD/CTSA Randomized Clinical Trial (RCT): Outcomes

Carol L. Wagner, Donna Johnson, Thomas C. Hulsey, Myla Ebeling, Judy Shary, Pamela G. Smith, Betty Bivens, Bruce W. Hollis. Pediatrics/Obstetrics, Medical University of SC, Charleston, SC.

BACKGROUND: Vitamin D (vitD) deficiency during pregnancy is a serious public health issue, affecting mother and fetus. Establishing optimal vitD requirements of pregnant women is vital in preventing vitD deficiency and its health-associated comorbidities.
OBJECTIVE: Evaluate the effectiveness of high dose vitD supplementation in decreasing pregnancy comorbidity risks.
DESIGN/METHODS: Following their consent, pregnant women 12-16 wks' gestation were randomized into 1 of 3 tx grps stratified by race: 400, 2000 or 4000 IU vitD₃/day until delivery. Women were evaluated for safety (Abstr#750939), efficacy and effectiveness with monthly 25(OH)D; 1,25(OH)₂D; serum Ca, Cr, phos, and urinary Ca/Cr levels, all measured using standardized methodology. Comorbidities of pregnancy (preeclampsia, gest diabetes, any infection, preterm labor (PTL)/preterm birth (PTB) <37 wks GA) were recorded prospectively for each subject. Investigators and health team were blinded to tx grp.
RESULTS: Of the 494 women who enrolled in the study, 350 women continued until delivery: 98 African American (AA), 137 Hispanic (Hisp) and 115 Caucasian (Cauc) women; with 111 controls, 122 in 2000 IU and 117 in 4000 IU groups. There were no differences in baseline vitD status between dose groups. The mean 25(OH)D by dose group at delivery, as chronic level, and 1-month before delivery were significantly different between control and 2000, control and 4000, and 2000 vs. 4000 (p<0.0001). 25(OH)D had a direct influence on 1,25(OH)₂D levels throughout pregnancy (p<0.0001) with 25(OH)D of 40 ng/mL required to obtain maximum 1,25(OH)₂D production. In bivariate analyses controlling for race, PTL/PTB and infection were inversely related to 25(OH)D and were lowest in the 4000 IU grp (p<0.0001). In logistic regression, comparing 400 vs. 4000 IU and controlling for race, the risk of comorbidities were 0.50 (CI 0.27-0.95; p=0.03) among those in the 4000 IU grp. Using least sq means, when adjusting for race, 25(OH)D of women with comorbidities was 33.4 ng/mL compared to 39.0 ng/mL in those women without (p < 0.008).
CONCLUSIONS: VitD sufficiency was strongly associated with decreased risk for PTL/PTB and infection during pregnancy and comorbities of pregnancy, with the greatest effect with 4000 IU vitamin D/day regimen. Therefore, to attain a minimal 25(OH)D level of 40 ng/mL, we recommend 4000 IU/day for all pregnant women.E-PAS20101665.6

Not that infection rates were inversely related to serum vitamin D levels.

Now, there used to be concerns over whether high vitamin D levels could cause birth defects related to calcium metabolism. The researchers found these claims to be baseless.

Vitamin D Supplementation during Pregnancy Part I NICHD/CTSA Randomized Clinical Trial (RCT): Safety Considerations

Carol L. Wagner, Donna Johnson, Thomas C. Hulsey, Myla Ebeling, Judy Shary, Pamela G. Smith, Betty Bivens, Bruce W. Hollis. Pediatrics, Medical University of SC, Charleston, SC.

BACKGROUND: Vitamin D (vitD) deficiency during pregnancy is a serious public health issue that affects both mother and fetus. Establishing the optimal vitD requirements of the pregnant woman is vital in preventing vitD deficiency.
OBJECTIVE: Evaluate the safety of high dose vitD supplementation during pregnancy in a RCT.
DESIGN/METHODS: Following their consent, pregnant women 12-16 wks' gestation were randomized into 1 of 3 treatment (tx) groups (grps) stratified by race: 400, 2000 or 4000 IU vitD₃/day until delivery. Women were evaluated for safety, efficacy and effectiveness with monthly 25(OH)D; 1,25(OH)₂D; serum Ca, Cr, phos, and urinary Ca/Cr levels, all measured using standardized methodology. Investigators & health team were blinded to tx grp.
RESULTS: Of the 494 women who enrolled in the study, 350 women continued until delivery: 98 African American, 137 Hispanic and 115 Caucasian women; with 111 controls, 122 in 2000 IU and 117 in 4000 IU grps. There were no differences in baseline 25(OH)D by dose grp. The mean 25(OH)D by dose grp at delivery, as chronic level, and 1-month before delivery were significantly different between control and 2000, control and 4000, and 2000 vs. 4000 (p<0.0001). 25(OH)D had a direct influence on 1,25(OH)₂D levels throughout pregnancy (p<0.0001). Throughout the study, there were no differences between grps on any safety measure: serum Ca, Cr, urinary Ca/Cr ratios (pNS between grps). Not a single adverse event was attributed to vitD supplementation by the DSMB. Neonatal 25(OH)D was significantly correlated with maternal 25(OH)D overall, 1-month prior and at delivery (r²=0.6; OR 0.50); and was significantly different by tx group: 18.2±10.1 (control), 22.8±9.8 (2000 IU) and 26.5±10.3 ng/mL (4000 IU), (p<0.0001).

An interesting pair of abstracts to be sure. I look forward to seeing the data for myself when it's published.

Silicon Nanowire Photovoltaics

2010-04-23T12:48:00.000-06:00

In the 14 February 2010 issues of Nature Materials, Kelzenburg et al. report on their progress in developing a photovoltaic cell composed of an array of Silicon nanowires: Enhanced absorption and carrier collection in Si wire arrays for photovoltaic applications. Also see the supplementary information on the fabrication process.

Theoretically an array of nanowires has some advantages over flat or patterned silcon when it comes to light trapping and absorption. The disadvantages come from difficultly in getting the electron-hole pairs out of the wires, both in having sufficient conductivity of the wires and a good electrical contact to the outside world. On the negative side using patterning requires some sort of controlled deposition onto the thin-film substrate when ideally you would like to use some sort of self-assembled system that doesn't require a carefully patterned mask and has a huge through-put for manufacturing.

Figure 1 from (Kelzenburg et al. 2010): (a) SEM image of regular nanowire array embedded in PDMS and (b) schematic of system.

The arrays in question are rods 8-12 μm long that cover 5 % of the areal density of the surface. Let's compare that to a wafer-type Silicon photovoltaic cell, which might have 250 μm of high-quality Silicon in it, the Silicon nanowire PV cell is using about 0.24 % as much material. Since photovoltaic-grade Silicon is quite expensive, this is potentially a cost advantage. From a practical perspective, this concept is robust because the silicon nanowires are embedded in a polymer that protects them from damage.

The authors also added aluminium oxide (Al₂O₃) nanoparticles to the sides of their nanowires in an effort to increase scattering within the cell and hence light trapping. This had a very significant effect and they achieved a maximum of 84.6 % of light absorption compared to 87.2 % for a commercial cell. Remember this is with a tiny fraction of the amount of Silicon used in a commercial cell.

Figure 4 (from Kelzenburg et al., 2010): Compare the solid red to solid blue lines in (a). The nanowire arrangement is slightly inferior in the visible spectrum but is markedly superior in the near-infrared. In (b) area under the curves indicates total light absorption and hence electron generation.

Designing the film so that the nanowires were oriented in a regular, periodic pattern gives a high packing fraction, thereby enhancing light absorption, but it also results in certain orientations being 'dead zones' where light is not well absorbed. In particular, when the rods are facing the sun dead-on, they do not absorb well. However, the regular array of wires would be well suited to situations where the photovoltaic panel was always oriented away from the sun, such as vertical mounts on a wall or horizontal mounts on a flat roof.

Lastly, it was reported at the end of the supplementary information (where better place to hide such details?) that they saw some evidence of sub-bandgap absorption. That is, light longer than 1120 nm was being absorbed. This isn't supposed to happen and it tends to reflect parasitic absorption that doesn't contribute to moving electrons (and in fact reduces the output current). Thus there is some concern that the increase in infrared absorption — the main claim to fame here — was due to parasitic effects rather than something that would actually enhance the electric current being produced. They did not, however, find that all of their cells had sub-bandgap absorption so it may be largely a quality control problem.

Chronic forms of Euthyroid Sick Syndrome and Non-Thyroidal Illness

2010-03-22T15:40:00.002-06:00

Introduction

Metabolism is the consumption of energy by a living organism. Basal metabolism is basically the sum of all energy the body uses to maintain its warm internal environment (37 °C or 98.6 °F nominally) in the face of the external environment. In essence, basal metabolism is the energy required to maintain homeostasis, and nothing else. Activity (walking, thinking) is considered to consume additional energy above basal metabolism.

Basal metabolism is measured via the proxy of body temperature and is said to represent the energy used to maintain a constant internal environment, known as homeostasis. Typically basal temperature itself cannot be measured so one measures 'resting' temperature first thing in the morning. For example, part of homeostasis in animals is movement to a more optimal environment, so where do you draw the line? The difference between resting and basal temperatures is a somewhat academic dispute that mostly has to do with the fact that body temperature follows a diurnal pattern, being lower at night while sleeping and higher in the day while active. This difference is a combination of higher cortisol activity and muscle motion during the day. Typically the night-time low cortisol state is regarded as the most reasonable approximation to basal temperature. Furthermore where you measure temperature matters. Armpit temperatures will be lower than sub-lingual (under the tongue) temperatures, which in turn will be lower than rectal or vaginal temperatures. Personally, I have a waking sub-lingual temperature of 36.5-.6 °C measured by a scientific mercury thermometer, which would solidly put me in the normal category at 37 °C internal temperature.

When we are talking about whether someone has a 'fast' or 'slow' metabolic rate we are usually referring to the concentration of active thyroid hormone in the major energy-consuming tissues, and not necessarily body temperature. Although the two are correlated, they are not the same thing. This is not to say that temperature doesn't matter, however, as most of the enzymes in your body have optimal activity close to 37 °C, which is why we evolved to maintain that particular internal temperature.

The thyroid hormone triiodothyronine (T₃) is a DNA transcription effector. That means that every time a cell in your body produces a messenger RNA that goes on to assemble a protein, there must be a T₃ molecule bound to the DNA (typically alongside several other gene regulators). T₃ is an enzyme, so it isn't destroyed by the process of transcription, but the concentration of T₃ is important in determining the rate of protein synthesis. Protein synthesis is a high energy consumption activity (around 9 kcal/g), so someone with poor basal hormone levels is going to have to do something else with that unused energy (i.e. fat storage) and there will also be less waste heat generated, so overall body temperature will decrease. Regulation of T₃levels is a complicated equilibrium process and I will try to explain it concisely and clear as I'm able.

Regulation of basal metabolism can be broken down into four basic components:

the hypothalamus/pituitary gland, which controls the negative feedback of the system and regulates the thyroid through thyrotropin (TSH);
the thyroid gland itself, which produces thyroxine (T₄);
the deiondinase system (D1, D2, and D3), which converts T₄to the metabolically active form triiodothyronine (T₃) in many diverse organs but especially the liver, skeletal muscle, the brain, and the thyroid itself, and D3 inactivates T_{3 to}T₂ in the liver;
the transport proteins, which are produced by the liver, which regulate the reservoir of T₄ and T₃ found in the blood (and hence their availability to tissues over seconds/hours/days timescales).

The axis of organs which dominate regulation of basal metabolism is the hypothalamus/pituitary/thyroid/liver. So whenever you have someone who self-diagnoses "hypothyroidism" any one of the above stages in the regulatory chain could be disrupted, and not necessarily the thyroid per se. An individual with poor basal metabolism but a healthy thyroid gland is usually referred to as having euthyroid sick syndrome, with the eu-prefix meaning true or normal. Another common synonym is non-thyroidal illness(es) often abbreviated NTI (de Groot, 1999). Euthyroid sick syndrome sometimes refers specifically to problems downstream of the thyroid (i.e. the deiodinases) and non-thyroidal illness to problems upstream (hypothalamus/pituitary) but the scientific literature is not consistent.

Kohrle (2000), provides an excellent quotation that underscores the complexity of the situation in how the literature on this subject is far too often confusing and contradictory,

As discussed above, complex superimposed and mutually interacting alterations of thyroid hormone economy are observed under these conditions: stress, activation of the pituitary-adrenal axis, inhibition of thyroid hormone production and secretion, changes in serum binding and distribution, tissue uptake and intracellular metabolism. Therefore it is not at all surprising, that different cellular or animal models and experimental manipulations provoking these syndromes led to divergent results.

Nominally non-thyroidal illness is considered an acute condition that passes with time (or kills the patient, acute NTI is very dangerous) but I strongly suspect that the same mechanisms can result in chronic conditions. My objective in this article is to explore how the basal metabolic system could potentially be disrupted in a chronic fashion to address the extremely common idiopathic “sub-clinical hypothyroidism” that I see evidence of far too often. The acute form of non-thyroidal illness often features a simultaneous lowering of TSH, T₄, and T₃ but all these features may not be present in more chronic conditions.

Hypothalamus
The headwaters of the basal metabolism control system starts in the hypothalamus, where a number of feedback mechanisms occur. When the hypothalamus determines that basal metabolism should be raised, it releasing thyrotropin-releasing hormone (TRH). TRH modulates the release of a number of other hormones (including prolactin, oxytocin, and arginine vasopressin) but primarily it stimulates the pituitary gland to produce thyrotropin (aka thyroid-stimulating hormone, TSH).

Leptin is one hormone that strongly influences the TRH neurons in the hypothalamus (Rogers, 2009). Individuals who were previously obese still have a greater than normal number of fat cells, with the result that circulating leptin levels are lower than one would otherwise guess from present body fat levels (Spalding, 2008). I have previously tried to make the case that formally-obese people may develop some of the symptoms of anorexia, in particular hyperactivity paired with lower thermogenesis, and potentially amenorrhea in women.

Aside from leptin, the TRH portion of the hypothalamus appears to be most sensitive to T₃. Many tissues have the ability to convert T₃ to T₄, but the hypothalamus isn't one of them. It is reliant on other tissues to produce T₃. Lechan and Fekete (2004) state that,

The source of nuclear T₃ responsible for feedback regulation of TRH neurons in the PVN (RM: paraventricular nucleus, a component of the hypothalamus) differs from the source of T₃ in other regions of the central nervous system (CNS) such as the cerebral cortex and anterior pituitary, where the majority of T₃ arises from the intracellular monodeiodination of T₄ to T₃ by type II iodothyronine 5'-monodeiodinase (D2) (62). This is because the PVN contains little, if any, D2 activity or D2 mRNA (63, 64).

The key take home point is that free T₃ in the bloodstream regulates TSH production (with at least one major exception), while many other parts of the body (e.g. skeletal muscle) which have an active deiodinase system may be more sensitive to T₄, which exists at much higher concentrations. I will discuss this further later on.

The Lechan group has followed up there results with an effort to see if inflammation can affect the TRH neurons directly (Sanchez, 2008). Cortisol may be considered the whole-body response to inflammation, and the Sanchez group did not find that it seriously impacted the TRH neuronal activity. They did, however, find that local inflammatory paracrine hormones (i.e. cytokines, which I like to refer to as immune system catnip) could turn on D2 genes found in specialized neuron supporting cells known as tanycytes (and they were hardly the first group to notice this association). Specifically, when they injected rats with bacterial lipopolysaccharide, the D2 activity in the tanycytes was turned on, and since these glial cells are adjacent neighbours to the TRH neurons we would expect the local T₃concentration in the TRH neurons to be higher. This in turn is going to down-regulate TSH production by the pituitary gland, as well as the other hormones the TRH neurons innervate (prolactin, oxytocin, and arginine vasopressin).

Lipopolysaccharide is a big word, so to simplify things just note that it is a component of bacterial cell walls, which are considerably different in composition from our cell membranes. Lipopolysaccharide is considered an endotoxin, and the two words are essentially synonyms as far as immunology is concerned. The innate immune system (neutrophils, macrophages, and natural-killer cells) can recognize it as hostile, and attacks. In general, I would expect the whole body to respond to an infection via a fever, so at first glance this feedback mechanism seems to be going the wrong way! However, we have to consider the evolutionary notion that all human cells might respond the same way, since bacteria don’t use thyroid-hormone as a DNA transcription activator. A bacterial infection in close proximity to the hypothalamus could result in down-regulation of TSH and hence T₄ levels. If an infection lasts a long time, then overall T₄ levels may be depleted over time and become depressed compared to normal. This is especially so because the rest of the body's D2 will also increase T₄ to T₃ conversion as a result of inflammatory signals triggered by the infection, thus depleting the T₄reservoir in the blood stream while simultaneously the thyroid is signaled to produce less T₄.

Chronic (aka latent) infections are quite possible, especially from organisms that are good at mimicking the host’s biochemistry and avoid total destruction at the hands of adapted immune system. In particular the Herpes family of viruses is well known for causing latent infections (e.g. see Grubor-Bauk, 2008 for where I am going with this), and I have previously made the case for chronic/latent bacterial infection causing atherosclerosis. Viruses have not yet been shown to cause the same effect, but they still cause a local inflammatory response. Sachez notes that, “Other mechanisms, such as an increase in proinflammatory cytokines, may be of primary importance in the D2 response to LPS,” so I feel reasonably safe in generalizing this phenomenon to viruses as well.

Interestingly there doesn’t appear to be a specific known system whereby the adapted immune system can recognize the hypothalamus as non-self tissue and attack, i.e. there is no known form of autoimmune hypo-hypothamalitis (it doesn’t exactly roll off the tongue now does it). Neurons are not supposed to be affected by the adapted immune system (T-cells and B cells), so the dogma says neurons should not suffer from autoimmune diseases. This is because neurons lack certain surface proteins, namely from the major histocompatibility complex (MHC). However, natural killer (NK) cells, which are part of the innate immune system but are really a variant of T cells, express different types of surface proteins, such as the KIR class (Cooley, 2006), and they are known to attack neurons and their accompanying cells (Hickey, 1992 and Darlington, 2008). If I can leave you all hanging for a couple months, I am pretty sure at this point that chronic fatigue and immune dysfunction syndrome/ myalgic encephalomyelitis/ fibromyalgia is precisely this pathology and is inducted largely by Epstein-Barr or cytomegalovirus infections that become latent in the hypothalamus.

Overall the endotoxin/LPS-induced dysfunction of the hypothalamus hypothesis seems to be strongest fit to hormone status for the actual case of acute non-thyroidal illness (de Groot, 2006) so I feel that this is probably one of the strongest potential pathologies for a chronic form of the same.

The Pituitary Gland
The pituitary is located directly underneath the hypothalamus but outside the blood-brain barrier, which enables it to discharge large quantities of peptide hormones into the bloodstream. Although the cell bodies of the TRH neurons are located in the hypothalamus, their axons (which is the long structure that action potentials are fired down) actually snake from the hypothalamus down into the pituitary, where they terminate. The separation between the TRH neurons and the thyrotropin (TSH) producing cells of the pituitary gland serves a couple of functions. One, the signal produces by the TRH neurons can be greatly amplified by having each of them stimulate many specialized endocrine cells. Second, the pituitary is outside the blood-brain barrier, which facilitates dumping relatively large peptide hormones into the blood. Incidentally, many of the hypothalamic neurons that penetrate into the posterior pituitary are essentially by-passing the blood-brain barrier. There are also channels from hypothalamus into the anterior pituitary, which is where all the major pituitary hormones are produced.

The pituitary itself can suffer from degenerative disease such as lymphocytic hypophysitis, which is an autoimmune condition of the pituitary gland (Rivera, 2006 and Crock et al. (Autoimmune Hypophysitis in “Autoimmune Disease in Endocrinology,” ed: A.P. Weetman, Humana Press, Totowa New Jersey (2008)). It also goes by other names, such as autoimmune hypopituatarism. There is also an atrophic form where the pituitary is shrunken and scarred by the autoimmune assault, known as granulomatous hypophysitis. When the pituitary is damaged typically more than one hormone is affected especially as the disease progresses. Adrenocorticotropin (ACTH) deficiency is the most common (60-60 %), followed by thyrotropin (TSH) deficiency (47 %), gonadotroponin (FSH/Lutein) deficiency (42 %), and growth hormone deficiency (42 %). Prolactin deficiency also manifests (34 %), possibly in conjunction with TSH deficiency. Headache is often associated with it, although that is a very non-specific symptom. Approximately 0.5 % of the population appears to be afflicted and I have to say, the quantity of research on this subject is seriously deficient considering just how many people must be affected. Autoimmune hypopitutarism is strongly associated with autoimmune thyroiditis, with perhaps 40 % of Hashimoto’s patients also having some degree of hypopituitarism.

I have used Table 1 before, and I present it again because it’s the best way I have to present the many functions of the pituitary gland without a massive wall of text. In general, when the pituitary isn’t functioning correctly, a huge variety of symptoms can present themselves.

Table 1: The hypothalamic/pituitary axis hormones and their actions on the human body.

Hypothalamus/Pituitary hormones	Description
Corticotropin-Releasing hormone (CRH) / Adrenocorticotropic hormone (ACTH)	Stimulates the adrenal glands to produce cortisol, a very important general stress hormone that among other things regulates activity of the immune system.
Growth-hormone Releasing Hormone (GHRH) / Growth-Hormone (GH)	Turns on fat metabolism and turns off protein and carbohydrate metabolism, putting the body in a fasted state. Circumstantially may stimulate production of insulin-like growth factor (IGF1) which is responsible for much protein synthesis in bone, skeletal muscle, and many other tissues.
Thyrotropin-Releasing Hormone (TRH) / Thyrotropin (TSH)	Stimulates the thyroid gland to produce T4, the inactive basal metabolism hormone. T3, the active form, is produced by seleno-deiodinases (D1, D2) found in many tissues but in humans predominately the liver and skeletal muscle. T3 is required for the transcription of all proteins (via messenger RNA) from DNA.
Gonadotropin-Releasing Hormone (GnRH) / Follicle-Stimulating Hormone (FSH)	Stimulates the gonads to mature germ cells (eggs and sperm)
Oxytocin (OT) / none	Neuropeptide that down-regulates activity of the amygdala, the anxiety-centre of the brain. Thought to have an important role in social cognition and mood, possibly responsible for “motherly” stereotypical behaviors. Also responsible for uterine contractions during childbirth and menstrual cramps. Can cause spontaneous miscarriage by this mechanism.
Arginine Vasopressin (AVP) / none	Triggers pair-bonding, jealousy, and other ‘male’ stereotypical behaviors. Also acts on the kidney to regulate water retention
Dopamine & TRH / Prolactin Hormone	Dopamine is the Prolactin inhibiting hormone while Thyrotropin-releasing hormone serves a dual role as the stimulating hormone. Prolactin is nominally responsible for lactation during breast feeding but perhaps more interesting is responsible for sexual satisfaction and orgasm in both men and women.
Gonadotropin-Releasing Hormone (GnRH) / Luteinizing Hormone	Triggers ovulation in females, with associated drop in estrogen and rise in progesterone. Triggers release of testosterone in males.

The headache and mass-effect symptoms (i.e. impaired vision) of hypophysitis may be associated with nausea, fatigue, and anorexia (lack of appetite). Hypophysitis often manifests after childbirth in the post-partum period, and in this case excessive production of prolactin (and hence breast milk) can occur analogous to Grave’s disease (hyperthyroidism). Lastly, diabetes insipidous is associated with hypophysitis, although lymphocyctic hypophysitis is usually considered to be a disease of the anterior pituitary gland. Diabetes insipidous occurs in the posterior pituitary, and involves dysfunction of arginine vasopressin, otherwise known as anti-diuretic hormone (ADH).

Diagnosis of hypopituitarism is challenging. Due to its location in the middle of the skull and small size, the pituitary is dangerous to biopsy. MRI can sometimes show an enlarged or shrunken pituitary gland. Low circulating levels of any of the pituitary hormones can indicate hypophysitis but they can also signal other problems with feedback in the hypothalamus or pathology of the hypothalamus proper. There is an anti-pituitary antibody test for lymphocytic hypophysitis but it is not very specific, likely due to the presence of five major forms of endocrine-hormone releasing tissue in the pituitary. One of the first groups to survey anti-pituitary antibodies (Stromberg, 1998) only found it in 28 % of their hypophysitis patients although test practices seems to have improved substantially since then by my reading of the literature. The link to celiac disease (below) seems to associate anti-pituitary antibodies with growth hormone deficiency in particular.

A hallmark of lymphocytic hypophysitis is atrophy of the gonads, adrenals, and thyroid gland. Endocrine tissue is much like muscle in that you either use it or lose it. If the pituitary isn’t stimulating these organs, they’ll shrink under the lesser workload, similar to how men who take synthetic testosterone have shrunken testes. This brings up an aside, that it’s difficult once a patient gets onto hormone-replacement therapy to get them back off, even if the autoimmune reaction is no-longer ongoing.

One of the more interesting associations of lymphocytic hypophysitis appears to be with celiac disease. If you are familiar with gluten sensitivity, you are probably aware that there are some idiopathic forms (i.e. those without known pathologies). An Italian group found that some 40 % of newly diagnosed celiac patients had anti-pituitary antibodies in their blood serum and it resulted in at minimum growth hormone deficiency (Delvecchio, 2010 and my post on the subject).

Thyroid Gland
Because one can find decent descriptions of hypothyroidism on the internet, I’ll not spend a great deal of time on this section, especially since I am interested in conditions where the thyroid works properly but basal metabolism is still depressed. The thyroid is a gland located on the throat that, under stimulation by TSH produces Thyroxine (T₄) from tyrosine amino acid residues. It also needs iodine, namely four atoms per hormone molecule (which is where the four-subscript comes from). The fabrication of T₄ is affected by two enzymes, thyroid peroxidase (TPO) and thyroglobulin (Tg).

There are two forms of autoimmune thyroiditis: Hashimoto’s, which is lymphocytic, meaning that the thyroid is so packed with immune system cells that it swells and presents as a goiter; and Ord’s, which is the chronic fibrosis form with an atrophied and scarred thyroid gland. Functionally Ord’s and Hashimoto’s appear to have similar outcomes, but present different symptoms. TPO antibodies typically indicate the goitergenic form while Tg antibodies alone indicate the atrophic form. TPO antibodies are considerably more common in Hashimoto’s thyroiditis than thyroglobulin antibodies. That unfortunately means Tg-antibodies often aren’t often tested for. Patients should be aware of this potential for false negative test results in autoimmune hypothyroidism, especially in conjunction with no goiter. If T₄ is low and TSH is high, make sure to get the Tg-antibody test if the TPO test comes back negative.

With the requirement of iodine, an element that can be in short supply in the diet, many people advocate supplementing with iodine especially if it isn’t taken in the form of iodized salt. However, I would be remiss if I didn’t mention that there is a strong body of research out there that shows that removing iodine from the diet can arrest hypothyroidism so I would caution people against taking large doses of iodine without being aware of the potential for an adverse outcome (Kasagi, 2003 and Yoon, 2003).

A number of dietary factors can also cause goiter and subclinical hypothyroidism. The main offender that I see mentioned in the literature is soybean protein products. The offending isoflavone found in products containing soy protein is called genistein (and to a lesser extent the isoflavone daidzein). Doerge and Chang (2000) found that genistein irreversibly bound to TPO and stopped its action permanently (in rats). They did not, however, find that T₄ levels were actually affected. Rather the production of TSH increased to induce the thyroid to build more TPO. Similarly another rat study found that the deiondinase system which converts T₄ to T₃ also increased its activity to compensate (Simmen, 2009, please note that no direct effect of genistein on hepatic gene regulation was demonstrated). Thus I conclude that reasonable quantities of goitrogens are safe for people with healthy basal metabolisms. On the other hand, if you are hypothyroid, why add additional stress on the system? This goitrogenic effect could still cause problems in a low-iodine environment, however, as iodine consumption also increased.

My main concern in this case is that soy (and other goitrogens) might actually induce autoimmune disease. If genistein binds irreversibly to TPO, it will change the shape/conformation of the TPO somewhat. If you are unlucky, a receptor on an immune B cell may then recognize the misshapen TPO as a foreign body and launch an autoimmune attack on the thyroid gland. This is the ‘superantigen’ hypothesis from autoimmunity theory. The positive news to take from this hypothesis, if you remove the goitrogen, then the autoimmunity should also go away (given half a year or more for the gland to start to heal assuming it hasn’t been completely obliterated by the immune system).

Aside from soy, some of the other goitrogens that I see in the literature include corn, the African staple crops cassava and millet, cruciferous vegetables (cabbage, broccoli, brussel sprouts, etc.), strawberries, and peanuts. Roman (2007) provides an exhaustive list of potential anti-thyroid agents (including pesticides and other environmental toxins) if the reader is inclined to investigate further.

Selenium Deiodinase Enzymes
Thyroxine (T₄) as produced by the thyroid is not a very effective in up-regulating DNA transcription. In order for it to be truly effective, one of the four iodine atoms attached to it must be removed, turning it into triiodothyronine (T₃). There are actually two forms of T₃, depending on which side of the thyroxine molecule the iodine is removed from, and only one of which is biologically active. The chemically active form has the iodine removed from the left-hand side, while the right-handed form is inactive, and is usually annotated rT₃ (standing for reverse T₃). The removal of a second iodine results in T₂, which is totally inactive.

Removal of iodine atoms is called deiodination, and it is accomplished by a set of globular protein enzymes know as the deiodinase family (Bianco, 2003 provides a detailed if technical review). The deiodinases feature an active site with a selenium atom, which acts to catalytically cleave off iodine atoms from the thyroxine hormone. Selenium is an essential element required for deiodinase fabrication. There are three known deiondinase enzymes, type 1 and type 2 (abbreviated D1 and D2) both convert T₄ to T₃ and can also deiodinate rT₃, so they cooperate as the on-switches Type 3 deiondinase (D3) deactivates T₄ to rT₃and both types of T₃ to T₂, so it acts as the off-switch.

D1 is found predominately in the liver and thyroid, as well as the kidney and pituitary gland and may be present in smaller quantities in other tissues. It is responsible for most of the circulating T₃, since the thyroid and liver are the primary exporters of thyroid hormone to the body. About 10 % of the T₄ produced by the thyroid is deiodinated before being released into the blood. D1 is a simplier complex compared to its cousin D2, and it is capable of producing either T₃ or the inactive form, rT₃, producing roughly equal quantities of both. The liver is also awesomely good at extracting thyroxine from the bloodstream, a point I will refer to in the thyroid transportation and storage section. D1 can produce T₃ much faster than D2 can (i.e. it has a high reaction velocity) but it requires a much higher concentration of T₄ which is probably why it is found predominately in the thyroid and liver.

D2 is predominately found in skeletal muscle, the heart, the brain and other nervous tissue as well as brown adipose tissue. D2 is apparently found in human thyroid tissue but not rat thyroids. It seems to have no proclivity to produce the inactive form rT₃, but like D1 it can inactivate rT₃ to T₂. D2 is capable of functioning at much (~1000x) lower concentrations of T₄ than D1 is (i.e. it has a high affinity for T₄). Otherwise it is similar in function to D1.

D3 historically was thought to be largely present only during childhood but there is plenty of research now that suggests that is not the case and that it is heavily expressed in the brain and skin (Kestler, 2006). After all, something has to inactivate T₃ to T₂, a point that some of the review articles I’ve read on the subject seem to have missed. Other research has pointed to activated immune system cells as potential sources for D3 activity (Boelen, 2008 and Boelen, 2009), which again points a potential finger at chronic infection/inflammation as a possible source of idiopathic hypothyroidism. One study published in the New England Journal of Medicine found that infantile hemangioma’s could grossly over-express D3 production, resulting in severe hypothyroidism (Huang, 2000). It’s also well known that placenta tissue expresses D3 heavily to protect the developing infant from the adult’s thyroid hormone levels, which could possibly account for post-partum hypothyroidism, but that is speculation on my part.

The D2 story is probably the most important from the point of view of a euthyroid sick syndrome. This is because local T₃concentrations in major tissues are determined by the local gene expression of the deiodinases, and not by blood T₃ levels (Kohrle, 2000). This is the reason for the heavy emphasis on circulating T₄ in testing for thyroid disorders. Thus the two principle requirements for maintaining a normal body temperature are:

Sufficiently high concentration of circulating T₄ in the blood.
Proper gene expression of the deiodinases.

Circulating T₃ is a proxy for D1 activity but not so much for D2 activity. It does interact with the hypothalamus as a feedback signal, but the majority of thermogenetic (heat producing) activity in the body is going to occur in the big energy-intensive tissues of striated muscle (including heart) (D2), brain (D2), and liver (D1). If a person has normal T₄ but a low basal temperature, the problem isn’t the thyroid.

The similar overlapping functions of D1 and D2 begs the question, what is the evolutionary significance of having two enzymes for the same function? As I’ve mentioned above, D2 seems to express in tissues that are required in survival situations: nervous and muscular tissue primarily. In comparison, D1 appears in tissues used for digestion (and presumably reproduction). On such a basis I would hypothesize that high stress will up-regulate D2 expression and down-regulate D1 expression.

Gene expression of the deiondinases is modified by a whole suite of hormones. Unfortunately, most of the data on this subject comes from rodents who have substantial differences in their deiodinase system compared to humans. For example, rodents do not produce D2 in their skeletal muscle, but humans do. I suspect much of the contradictory results in the research surrounding the selenium deiodinase activity are due to interspecies variation, and variation amongst rodent lines. Nonetheless, I present the data for rodents in Table 2, but please be aware it may be flat-out wrong.

Table 2: General effects of endocrine hormones on D1 and D2 activity in humans (from Bianco and Kohrle)

Hormone	Effect on D1 activity	Effect on D2 activity
Androgens (testosterone)	Increases (tissue specific – liver)	Unknown
Estrogens (estradiol)	Increases (tissue specific	Unknown
Glucocortoroids (cortisol)	Decreases	Trivial increase
Catecholamines (adrenalines)	Unknown	Increases
Growth hormone (GH) & Insulin-like growth factor (IGF-1)	Increases ratio of T₃ to T₄ and reduces rT₃; could also be down-regulating D3	Unknown, likely similar to D1
Thyrotropin (TSH)	Up-regulates thyroid D1 indirectly	Increases
Cytokines (i.e. ‘inflammation’)	Decreases	Increases
Insulin	Increases	Increases
Glucagon	Decreases	Unknown
Cold exposure	Increases	Increases

Reverse T₃ is an interesting molecule that could potentially cause a lot of problems if the balance of T₃ to rT₃ was overly altered. It acts as a highly competitive inhibitor for the T₃ in DNA transcription, which means it gets into T₃ spot but it doesn’t cause the correct shape changes that allows DNA to be copied into RNA. It’s likely very difficult to tell rT₃ from T₃ in the lab since they have the same molecular weight and very similar chemistry (e.g. Zhang, 2005), such that your average commercial lab cannot tell the difference. Both D1 and D2 do remove rT₃ by transforming it to T₂ so it is not clear at all whether rT₃ can cause physiological problems. When considering D1 alone there should be some steady state quantity of rT₃ in tissues that are served by thyroid and liver-derived T₃. I personally suspect rT₃ is involved in the local regulation of T₃, in that it prevents local tissues that produce T₃ for export to the body from overwhelming their oxygen and nutrient supplies.

I did find one mention for potential pathology for rT₃ from wikipedia:

rT3, unlike T3, does not stimulate thyroid hormone receptors. However, rT3 nonetheless binds to these receptors, thereby blocking the action of T3. Under stress conditions, the adrenal glands produce excess amounts of cortisol. Cortisol inhibits the conversion of T4 to T3, thus shunting T4 conversion from T3 towards rT3. Consequently, there is a widespread shutdown in T3 binding across the body. This condition is termed Reverse T3 Dominance. It results in reduced body temperature, which slows the action of many enzymes, leading to a clinical syndrome, Multiple Enzyme Dysfunction, which produces the effects seen in hypothyroidism. Effects include fatigue, headache, migraine, PMS, irritability, fluid retention, anxiety and panic.

The only scientific literature I was able to find on this subject was in the Puerto Rico health sciences journal, which seems a strange place for a doctor from Vermont to publish (Friedman, 2006). Personally, I am inclined to treat Wilson’s thyroid syndrome as a wikipedism for now as I am unclear on how cortisol could directly affect the conversion of T₄ to rT₃ unless it is capable of directly binding to D1 in an allosteric fashion.

One potential link to autoimmunity has been the discovery of anti-D2 peptide antibodies and the fact that they are commonly found in association with anti-pituitary antibodies (Nakahara, 2005). They found 32 % of their Hashimoto’s patients had anti-pituitary antibodies and 27 % had anti-D2 peptide antibodies, with only a weak correlation between the two (R² = 0.33). The researchers apparently thought that D2 could be the antigen for the anti-pituitary antibody but their results didn’t support their hypothesis very well. This underscores a point that I would like to make: Hashimoto’s thyroiditis may have consequences that extend outside of the thyroid in a large minority of patients, so if T₄ replacement therapy doesn’t provide relief for symptoms, then there may be problems upstream or downstream of the thyroid gland. Autoimmune diseases have a tendency to cluster.

From my reading of many of the articles relating to the deiodinases it does seem clear that fasting will decrease thermogenesis (Coppola, 2005) and in particular serum T₃ decreases, but should only do so in a transitory fashion. I plan to return to this topic at a later date, since it requires a more in-depth discussion than I want to provide in this review. The implication from my point of view is that while circulating T₃ drops during fasting, the brain, heart, and skeletal muscle, which all rely on D2, will be less affected and this seems to lead to hyperactivity, so the net effect on caloric expenditure may be minor. For most people, fasting remains a good was to restore heath to a damaged liver but if you have low T₃ blood levels avoid fasting as a weight-loss technique.

Transport and Storage of Thyroid Hormones in the Blood
This last section is largely regarding the role of the liver in basal metabolism. Many diseases of the liver are associated with poor thyroid function (Malik, 2002), including cirrhosis. Malik’s article also makes the point that α-interferon, sometimes used as an antiviral drug, can induce autoimmune diseases including hypothyroidism. In addition to producing more serum T₃ than any other organ, including the thyroid, the liver is also responsible for fabricating all the proteins that transport thyroid hormone in the blood.

Many hormones in the blood that are not water soluble (especially steroids and thyroid hormones, which are lipids) are often bound to transport proteins, specifically thyroxine-binding globulin (TBG), albumin, and transthyretin (aka prealbumin). Through random chance, some hormones dissociate and some bind such that equilibrium is formed between bound and unbound hormone. Typically only 0.02 % of T₄ and 0.3 % of T₃ in the blood is actually unbound. Typically 75-80 % is bound to TBG, 15-20 % to transthyretin, and 5-10 % to albumin.

The free hormone hypothesis states that only the unbound (or free) concentrations of thyroid hormones are important to determine concentration inside the cells of body tissues. However, the three transporting hormones have differing properties and the free hormone hypothesis misses some key points. First, the binding half-lives for albumin and transthyretin are considerably shorter than TBG, so when in the capillary bed, as the free hormone is taken up by tissues that which is bound to albumin and transthyretin will tend to dissociate to restore the equilibrium (Fig. 1). This acts to keep the concentration of free thyroid hormone constant as the blood passes through the capillary bed, so that tissues more on the venous side of the circulatory system are not thyroid-hormone deprived. In this case, the amount of bound thyroid hormone also matters. This is known as the free hormone transport hypothesis and is almost exclusively the brainchild of Mendel, 1992. Depending on the length of the capillary bed that feeds them, different tissues may be more or less sensitive to either unbound or bound thyroid-hormone concentrations.

Figure 1: (A) Dissociation rate of T₄ from transthyretin and, (B) from thyroxine-binding globulin (TBG) (from Mendel, 1988). Typically it takes 60 seconds for blood to circulate.

The liver actually uptakes an amazing amount of the total T₄ in the blood, about 10-12 % per pass. Note this is not 10 - 12 % of the free T₄, but 10-12 % of all T₄ including bound T₄ that passes through the portal vein, which in turn is about 20 % of the blood supply. That means literally the liver is up-taking about two-hundred times the total available free T4, every time the blood circulates past. It doesn’t take a genius to realize that this means that free thyroid hormone levels are not the be all and end all. As you might expect from this result, the liver has the ability to pick-up thyroid hormone in the bound form (i.e. attached to serum proteins) directly from the blood.

Where Mendel was going with his line of thinking appears to have been that an upset in the balance of binding affinities (i.e. too much TBG compared to transthyretin) could reduce the rate at which T₄ diffuses into the tissues and hence be a potential cause of non-thyroidal illness (Mendel, 1991). Alternatively other serum molecules in sick patients could bind to the thyroid-binding proteins (either at the binding site or somewhere else), radically changing their affinity to thyroid-hormone such that they hold onto it far too tightly or not at all. Overall, Mendel’s results were negative for a binding inhibitor but some other research has suggested that free-fatty acids (FFA) as a possible culprit (Chopra, 1986). Recall that free-fatty acids are often a product of a fatty liver overburdened with fructose intake. Other research found that bilirubin could act to inhibit uptake of T₄ into the liver (Lim, 1993). Research in this area seems to have petered out over the last decade; if there are effects, they may be indirect and not causative.

Conclusion

Overall, there is a fair amount of evidence to suggest that autoimmune hypothyroditis may have additional complications beyond the thyroid-gland itself, or that chronic conditions may be resulting in poor basal metabolism even with euthyroid status. This seems particularly evident for potential problems upstream of the thyroid, in the hypothalamic/pituitary axis. The deiondinase system is also very likely to be a source of problems, particularly with regard to the many factors that regulate it. The main trouble with diagnosing problems with the deiodinase system is that it is very complicated and much of the data are contradictory. This area will continue to develop and perhaps over the next five years the picture will be much clearer than it is now.

This review is not even close to exhaustive; that would require a book. For those of you with unresolved basal metabolism problems I hope I have provided you with some food for thought to try and resolve them. On the other hand, if you are a hypochondriac you probably should have stopped reading at the title. Sorry.

40 % of Celiac Patients have Anti-Pituitary Gland Antibodies

2010-03-13T18:40:00.001-07:00

In 2006, an Italian group noted that children with celiac disease often suffered from failure to thrive (i.e. they were short and slight) (Iughetti, 2006). They were able to link this to a deficiency in growth hormone, which is produced by the pituitary gland. Now, growth hormone itself doesn't regulate bone growth, but insulin-like growth factor-1 (IGF-1) does and it is regulated by growth hormone. After removing gluten from the diet, most children had a growth spurt and caught up to their peers but seven did not. Those that didn't catch up were then tested for anti-pituitary antibodies, and five of the seven presented them.

Now 5 of 7 is not a sufficient statistical sample, so the group went back to work over the next three years and tested for anti-pituitary antibodies in many of their newly diagnosed celiac patients (all children) (Delvicchio, 2009, also see editorial by Fasano, 2010). 50 of 119 (42 %) tested positive for anti-pituitary antibodies. There is an interesting comment by Delvicchio to the extent shortness can appear independently of the destruction of intestinal vilae,

It is well established that short stature can be the only presenting clinical feature of CD (31) and in unselected cases admitted for short stature, the prevalence of CD reaches 8%, CD being by far more common than GHD or any other organic disorder. The pathogenesis of CD-associated short stature is still unclear and although growth retardation has traditionally been attributed to generalized or selective malnutrition, new insights on its pathogenesis are emerging.

This suggests that something like one in ten children who are short are short because they eat wheat (notwithstanding selection bias). This isn't the first time autoimmune disease of the pituitary gland has been linked to stunted growth either. A child with lymphocytic hypophysitis (including diabetes insipidus) was previously found to have the same bone-age retardation symptoms as the celiac patients (Weimann, 1997).

The pituitary gland is a small bulbous organ that sits at the base of the brain smack dab in the middle of the skull. The pituitary is often called the master endocrine gland, but it is in turn is controlled by the hypothalamus, a portion of the brain that is the nexus of the autonomic nervous system. The hypothalamus, the posterior pituitary, and the anterior pituitary can all be considered to be different tissues of a single organ system often called the hypothalamic/pituitary axis. Because the pituitary controls such a diverse set of endocrine tissues, if something goes wrong with the hypothalamus/pituitary axis the symptoms can be very diverse. Furthermore, the area is small, located in the center of the skull and hence largely impossible to safely biopsy.

Like other endocrine organs, the pituitary can be victim to the helper and killer T cells of the adapted immune system. This condition is typically called lymphocytic hypophysitis, but also autoimmune hypopitutarism, and typically affects the anterior pituitary which is the hormone-producing portion of the pituitary (Rivera, 2006). The neural portion of the pituitary, the posterior portion, can also be affected and this typically causes diabetes insipidus through arginine vasopressin deficiency (not to be confused with the insulin disorder diabetes mellitus). Autoimmune disease of the pituitary gland is thought to be quite uncommon, with a series of 2500 surgical cases finding an incidence of 0.24 % (6 of 2500) (Sautner, 1995).

Although the Italians appear to have examined primarily growth hormone deficiency, lymphocytic hypophysitis usually results in more than one hormonal deficiency. Rivera (2006) notes in a review for lymphocytic hypophysitis that 60-65 % of cases have ACTH deficiency, 47 % have TSH deficiency, 42 % have gonadotropin deficiency, 37 % growth hormone deficiency, and 34 % prolactin deficiency. For those of you who aren't familiar with the hypothalamus/pituitary hormones I present the following summarizing table:

Table 1: The hypothalamic/pituitary axis hormones and their actions on the human body.

Hypothalamus/Pituitary hormones	Description
Corticotropin-Releasing hormone (CRH) / Adrenocorticotropic hormone (ACTH)	Stimulates the adrenal glands to produce cortisol, a very important general stress hormone that among other things regulates activity of the immune system.
Growth-hormone Releasing Hormone (GHRH) / Growth-Hormone (GH)	Turns on fat metabolism and turns off protein and carbohydrate metabolism, putting the body in a fasted state. Circumstantially may stimulate production of insulin-like growth factor (IGF1) which is responsible for much protein synthesis in bone, skeletal muscle, and many other tissues.
Thyrotropin-Releasing Hormone (TRH) / Thyrotropin (TSH)	Stimulates the thyroid gland to produce T4, the inactive basal metabolism hormone. T3, the active form, is produced by seleno-deiodinases (D1, D2) found in many tissues but in humans predominately the liver and skeletal muscle. T3 is required for the transcription of all proteins (via messenger RNA) from DNA.
Gonadotropin-Releasing Hormone (GnRH) / Follicle-Stimulating Hormone (FSH)	Stimulates the gonads to mature germ cells (eggs and sperm)
Oxytocin (OT) / none	Neuropeptide that down-regulates activity of the amygdala, the anxiety-centre of the brain. Thought to have an important role in social cognition and mood, possibly responsible for “motherly” stereotypical behaviors. Also responsible for uterine contractions during childbirth and menstrual cramps. Can cause spontaneous miscarriage by this mechanism.
Arginine Vasopressin (AVP) / none	Triggers pair-bonding, jealousy, and other ‘male’ stereotypical behaviors. Also acts on the kidney to regulate water retention
Dopamine & TRH / Prolactin Hormone	Dopamine is the Prolactin inhibiting hormone while Thyrotropin-releasing hormone serves a dual role as the stimulating hormone. Prolactin is nominally responsible for lactation during breast feeding but perhaps more interesting is responsible for sexual satisfaction and orgasm in both men and women.
Gonadotropin-Releasing Hormone (GnRH) / Luteinizing Hormone	Triggers ovulation in females, with associated drop in estrogen and rise in progesterone. Triggers release of testosterone in males.

The study did test for thyrotropin (TSH) and didn't find any significant association between anti-pituitary antibodies and basal metabolic dysfunction at the hypothalamus/pituitary axis. However, some 10 % of the patient population did have thyroid disease which is far above the general population average (of around 1 %). Hypophysitis tends to develop over time, with more and more functions being damaged, so these results may simply be representative of the young age of the patients (average age was ~ 6 years old).

In general, persons with one autoimmune disorder are at much higher risk to develop other immune disorders. It would take more effort and text to explain why this is than I'm willing to expand here so I will simply claim this is a fact. It seems that Iughetti has been on the case of co-morbid endocrine disorders associated with celiac disease for quite awhile (Iughetti, 2003). If you go to the Wikipedia page for gluten sensitivity you will see an entire section on "idiopathic gluten-sensitivity." A lot of this could possibly be traced back to autoimmune disease of the pituitary gland.

I recall that something like 12 % of the general population present anti-gliadin antibodies (gliadin being the offending peptide found in the wheat gluten protein). Celiac disease is only one manifestation of gluten sensitivity and I am quite certain that we will continue to see new conditions linked to gluten sensitivity over the next couple of decades. The secondary plant compounds found in the wheat plant's seed seem to be quite harmful to humans and in my opinion wheat is not suitable for human consumption. Plants, after all, cannot run away so they must rely on armour and toxins to stop animals from eating them. Anyone suffering from an unknown condition that presents as a disrupted hormonal milleu should strongly consider the shotgun approach of a paleolithic diet as a potential solution.

Degenerative and man-made diseases in the developing world

2010-02-12T16:12:00.003-07:00

I came across a relatively recent article by Kuper and Kuper in the Financial Times on the rise of degenerative and man-made diseases in the developing world that I suggest reading. The advent of smoking and low-quality industrial food is making many of the world's poor less healthy even as medicine manages to fight back infectious diseases around the globe.

This paragraph, however, made me laugh:

We now know that Omran failed to foresee a fourth stage of the transition: the decline of chronic diseases. The west – and particularly its richest inhabitants – has now reached this stage. Thanks to the “cardiovascular revolution” – the medical advances in treatment – the past 30 years have seen death rates from heart disease fall by 70 per cent in the US, the UK, Australia, Canada and Japan. That translates as 14 million American and eight million British lives saved between 1970 and 2000.

Part of the problem with modern medicine is that mortality trumps morbidity, every time in funding, in research effort, and in much every aspect of the system. Eventually I think the system will figure things out, but there's a lot of inertia to overcome as well as moneyed interests who benefit from people in poor health. The whole article is really a great example of the common wisdom facilities that need to be overturned so we can get anywhere.

I have been a little snowed under lately with work so no substantive posts. I am going surfing in Tofino for reading week, maybe I will work up a post while I am away, or maybe not...

Foxa2 Transcription Factor Implicates Direct Role for Insulin in Hunger

2010-01-18T21:12:00.002-07:00

Insulin has a number of down-stream targets (receptors), one of which has the highly descriptive name foxa2 (aka hepatocyte nuclear factor 3-beta). This receptor is closely tied to the liver and how it reacts to insulin (Wolfrum, 2004). Essentially foxa2 is one of the regulators responsible for the production of enzymes that are involved in beta-oxidation of fatty acids and the production of ketones. Insulin binds to foxa2, making it unable to perform its function in activating the production of these important fatty-acid metabolism enzymes. In this manner, insulin shuts down fatty acid metabolism.

First a little background on gene expression if you didn't implicitly understand what I wrote above. About 1 % or so of your DNA encodes for proteins. To make a protein, the DNA has to be pulled apart and a complementary single-stranded RNA polymer built to match. This is called messenger RNA and it is sent off to an organelle known as a ribosome which actually assembles the protein that the DNA encodes for.

The rest of your DNA is functional with 'dead space' being a common function. DNA, when being unzipped typically folds in on itself, so sections of the DNA well ahead of the protein encoding region often have functions related whether or not that protein encoding region is actively being transcribed or not. Other proteins literally sit on these spaces and their interaction with the enzymes that unzip and transcribe DNA determine whether messenger RNA is produced or not. Foxa2 is one of these gene transcription activators, so it operates at a very basic level of cellular mechanics. However, it can only do this when insulin is bound to foxa2. Presumably the binding of insulin to foxa2 reconfigures the shape of the foxa2 protein; with proteins, function follows structure/shape.

Silva et al. (2009) published in the journal Nature that this same receptor, foxa2, is found in the hypothalamus (of mice) and it directly effects the hunger reflex. What they did was to take normal and genetically obese mice, fast them, and inject some of them with insulin to put them into the 'fed' state. They then sacrificed the mice and dissected their brains, using an antibody-based stain to identify neurons that were positive for foxa2 and orexin and melanin-concentrating hormone (MCH). Orexin and MCH are known to be associated with feeding and, incidentally, sleep behaviour (Willie, 2001). From their results the authors concluded that the production of the neuropeptides orexin and melanin-concentrating hormone (MCH) were promoted by the foxa2 receptor (but only with insulin attached to it). One of the stronger pieces of evidence was that foxa2 was found in the cytoplasm of the mouse neurons when in the fasted state but in the nucleus when in the fed state. Transcription of messenger RNA occurs in the nucleus.

Supplementary Figure 1 (from Silva, 2009): Author's impression on how the foxa2 receptor cycles in and out of the nucleus in response to insulin.

I put mice in parenthesis in the preceding paragraph because there have been significant differences found between how various pieces of molecular machinery are distributed in rodents versus humans. A good example of this is selano-deiondinase type 2 (D2), which converts the inactive form of thyroid hormone, T4, into the active form T3. It's found in the skeletal muscle of humans but not rats ( Heemstra, 2009 and Larsen, 2009). Incidentally, both papers have fascinating implications for fasting in humans as well as sick euthyroid syndrome.

Interestingly the way they found the distribution of the Foxa2 receptor amongst neurons of the hypothalamus was through the use of specific antibodies as a microscopy fluorescence stain. I'm not clear on how these antibodies are fabricated from the supplemental literature, and a search for, "foxa antibod*" on PubMed didn't return any pertinent hits. I'm sure this is a common method as I've seen it before in fluorescence microscopy, but I am curious about the potential for an associated autoimmune disease.

If you read my previous post on leptin and anorexia (01/12/2010), there is additional support in Silva for the notion of hyperactivity in a fasted state:

Interestingly, the Nes-Cre/+;Foxa2T156A^flox^/flox allele was associated with dramatic increases in spontaneous locomotor activity relative to control mice (Fig. 3i). The difference between the locomotor activity of Nes-Cre/+;Foxa2T156A^flox^/flox mice and that of Foxa2T156A^flox^/flox or Nes-Cre/+ mice was similar to the increase in movement of fasted wild-type mice relative to fed wild-type mice (Fig. 3j). The types of physical activity induced in Nes-Cre/+;Foxa2T156A^flox^/flox mice included searching as well as intense grooming, rearing and face-washing behaviour.

If you can get past the ridiculous names of the mice variants, the English here is pretty clear.

Now it's very easy to get lost in minutiae such as this and lose clarity in the process. Of course, minutiae does have value for the task of bamboozlement. If we pull back and look at the big picture, the key point here is that insulin has been directly implicated in the hunger reflex for the first time, to my knowledge. Previously I assumed that only leptin and ghrelin can effect hunger. Now, when I read this article I did ask the question, has insulin been implicated to interact with this receptor at a biochemical level, or perhaps it is stimulating some other intermediate hormone which in turn interacts with foxa2? The answer is, yes, insulin is the actor and it directly binds to foxa2 (Wolfrum, 2003).

Leptin and Anorexia

2010-01-12T16:53:00.002-07:00

I have, off and on, entered into discussions with other bloggers on the role of leptin in long-term energy storage. Leptin, we know, is strongly related to long-term storage of fat and is probably one of the primary hormones associated with obesity (Kelesidis, 2006). It is thought, along with ghrelin, to be one of the hormones responsible for appetite.

One question I've posed is does leptin have an antagonist hormone? Most hormones have complements that act to oppose their action. For example, insulin versus glucagon/growth hormone. As an aside, please recall that growth hormone is primarily a catabolic hormone that turns on the body's fat metabolism, a state we call fasted. Generally an antagonist allows the endocrine system to respond more rapidly than simply waiting for the pertinent hormone's concentration in the blood to clear. Does leptin need an antagonist? Or does it operate over such a long time-span that it normally wouldn't need one? Is the lack of an (apparent) antagonist perhaps one of the reasons leptin metabolism can go screwy?

As an alternative to looking into why leptin makes people fat, I thought it might be interesting to examine how a lack of leptin makes people skinny, or anorexic. Anorexia just ~~means 'skinny'~~ refers to a lack of appetite in medical parlance, while anorexia nervosa (AN) refers specifically to the eating disorder that we've all heard about in the news. People can have abnormally low-body fat without having an eating disorder. For example, individuals with cortisol insufficiency (such as Addison's disease, an autoimmune condition involving destruction of the adrenal cortex) tend to have very low body fat levels, but not necessarily a lack of lean body mass. The lack of cortisol just mutes the body's stress response to store an emergency reserve of fat.

One of the markers that characterizes anorexia nervosa is low circulating leptin levels.

Now, leptin likes to interface with the hypothalamus, which is the part of your brain that essentially acts as an interface between the digital-fast (neural) and analogue-slow (endocrine) control systems of the human body. Lot's of things like to interface with the hypothalamus though, so please do not take this role of leptin as dogma. Together, the hypothalamus and pituitary are the master endocrine organ system, regulating the serum concentration of most of the hormones in your body. Essentially it integrates many different signals, and based on those signals decides what quantity of eight primary hormones to release (i.e. oxytocin, argigine vassopressin, adrenocorticotropic hormone, growth-hormone, thyrotropin (TSH), prolactin, luteinizing hormone, and follicle-stimulating hormone). The hypothalamus plays a crucial role in regulating immune function, metabolism, sex function, and mood/anxiety amongst many others.

The hypothalamus (and the pituitary by extension) tends to release hormones in pulses. When I say the hypothalamus exists on the border between digital and analogue that is nearly literally true. The hypothalamus samples the blood-stream for various feedback mechanisms (i.e. hormones) and when it adds together enough signals that indicate the system needs more growth hormone, it generates a pulse. This is done by the combination of neural and endocrine tissues. Leptin is one of the signals that contributes to whether or not pulses are released from the hypothalamus. If everyone's leptin receptor cells are identical, which is not likely, then low leptin levels will probably down-regulate some of the hypothalamic-pituitary hormones and up-regulate some others, while high leptin levels will do the opposite.

One very common side-effect of AN is the loss of the menstrual cycle (which has the scientific name amenorrhea) The menstrual cycle is initiated by a luteinizing hormone pulse, which implies that very low leptin levels have effects beyond simply regulating fat levels. This is not a surprising result; we would expect the body to shut down non-essential functions when it is starving. This result is correlated to circulating leptin levels (Blüher, 2007). Blüher has some interesting comments on the matter of leptin release:

Leptin secretion can be stimulated by insulin, glucocorticoids (RM: cortisol), and cytokines (RM: immune system catnip) (i.e. tumor necrosis factor [alpha]), whereas catecholamines (RM: "adrenaline"), free fatty acids, cold exposure and thyroid hormones inhibit leptin release [18,19]. Estrogens induce leptin production whereas androgens (RM: male sex hormones) suppress it, providing an explanation for the sexual dimorphism in serum leptin levels [19]. Although anthropometric and clinical features (gender, fat mass/fat distribution, hormones and cytokines) may influence the secretion pattern of leptin, the crucial factor in regulating serum leptin levels seems to be caloric intake and the amount of energy stored in adipocytes [5].

Another side-effect of AN is increased activity (aka hyperactivity), which is a homeostatic method to increase caloric expenditure. This is called activity-based anorexia (ABA) and is one of the primary animal models of anorexia. A review by Hillebrand et al. (2008) shows that leptin itself appears to be signaling the hypothalamus to encourage the brain to engage in this sort of behaviour, and that leptin-replacement therapy suppressed this activity. It's been hypothesized that hyperactivity would promote foraging behaviour in the paleolithic-era and in wild animals. Leptin also has a role in the homeostatic mechanisms behind thermogenesis via the basal metabolism of the thyroid hormones and brown adipose tissue (Rogers, 2009).

This result begs the question, are obese individuals sedentary because they have high circulating leptin levels? Was Gary Taubes, of Good Calories, Bad Calories fame, right in the lack of a relationship between exercise and obesity, even if he didn't know why? If so, hyper/hypoactivity as it relates to leptin would appear to be a case of positive feedback, where the signal tends to reinforce itself over time. It's only because gathering food requires so little energy investment today (get off couch, walk to pantry, grab chips) that this positive feedback cycle blows up so spectacularly. Historically putting on some fat might discourage activity via leptin, giving the organism a rest period.

Now on another front, anorexia nervosa patients who recover from the condition and regain body weight often regain too much and become overweight. This occurred even when caloric-intake and leptin levels were monitored during the body weight gain period to prevent excessive weight gain (Lob, 2003). So once again we see the dominance of the endocrine system and homeostasis over counting calories.

What might cause this higher than normal set-point of body mass index (BMI)? This question does not seem to have a firm answer quite yet so I'm going to speculate. The hypothalamus is a union of neural and endocrine tissue. Neurons, in particular, are quite plastic in that the amount of stimulus you have to apply to get them to fire changes depending on their exposure history. This is how memory is thought to work, for example. My hypothesis is that the neural component of the hypothalamus habituates to long-term leptin exposure.

There are clearly some threshold levels where leptin indicates an organism is in semi-starvation mode and generates compensatory behaviour (Müller, 2009). I can postulate that there may also be hibernation morphology at the top-end of the leptin spectrum. If the organism stays in semi-starvation mode for long enough, perhaps the sensitivity to leptin in the hypothalamus is reduced by the plasticity of the neural component. In this case, a crash weight-gain diet would not give the hypothalamus's neurons sufficient time to change their sensitivity to leptin, and adapt a new set point.

Maybe this is the reason why fast weight-loss programs typically fail miserably. The leptin set points for semi-starvation modes are at at abnormal levels, and pushing leptin through them induces behaviour that likely results in a rebound. The solution then is to be patient and go slow with weight loss or gain. If my hypothesis is correct, losing weight too fast may actually permanently distort leptin regulation.

Composition of Gut Biofilms

2009-12-16T23:55:00.001-07:00

There was a very interesting article published in the 05 November 2009 issue of Science magazine on the composition of bacterial colonies in humans. A human has more bacterial cells living in and on it than it does have human cells. Costello et al. (2009) (also see Supplemental Online Material which I think is free access and comprises 90 % of the article) took bacterial samples from 7-9 humans (likely the authors' themselves) over several months to assess both the composition of bacterial colonies from various sites such as the gut, forehead, and nostril, and to assess whether the composition changed with time. They found significant variation from person to person but not a lot of change over time. Hence the notion that we all have our own individual bacterial flora.

Table 1: Average composition of bacteria in human gut

Gut Bacteria Phylum	Proportion of Nucleotide Sequences (approximate %)
Firmicutes	35
Proteobacteria	5
Bacteroidetes	60
Verrucomicrobia	0.24
Lentisphaerae	0.05

Bacteria on the surface of the various membranes that separate our innards from our environment are essentially the first line of defense against intruders. They form more or less continuous biofilms consisting of bacteria held together by a matrix of congealing substance, such as mucous. Bacteria colonies on our bodies are mostly symbiotic, although they can be parasitic at which point they become pathogens. So there are 'good' and 'bad' bacteria. What determines whether we have mostly 'good' symbiotic bacteria or not? How do we encourage the development of 'good' bacterial flora and discourage harmful flora? Good bacteria can out-compete pathogens, predigest anti-nutrients before they can penetrate the gut lining, thereby providing useful symbiotic services to us.

These are questions I do not have answers to, but I do have hypotheses.

Bacteria are prokaryotes, which means they are much much smaller and simpler than any one of our cells in our body. In fact they are about the same size as the mitochondria organelles in our cells. Mitochondria are the ATP-producing energy factories of our cells, and all they do is break apart fatty acids (called beta-oxidation) and oxidize Acetyl-CoA, the produce of beta-oxidation and glycolysis of glucose. A bacterium has to to all that and more all in a small package. As a result, bacteria often can only exist on certain nutrients: lactose, glucose, fatty-acids with a certain number of carbons, etc. These are called metabolic pathways, and they represent a specific set of chemical reactions that eventually result in the production of ATP, the energy currency of living things.

The obvious conclusion to draw here is that macronutrient ratios will likely be fairly important for determining the composition of gut flora, but it will not be a question of carbohydrate versus fat. It will be a question of 4-chain saturated fatty acids versus 18-chain monounsaturates, glucose versus fructose versus galactose, because that's the level of detail required for metabolic pathways. In addition, there is almost certain to be some synergy between various forms of bacteria when they form little symbiotic colonies, with one living off the metabolic produces of the other.

Micronutrients may also matter to gut biofilm composition. Most biochemical processes in the body require enzymes to catalyze the reaction. Enzymes are usually protein chains in which one amino acid group has had a elemental substitution that acts as an active site with chemical activity. An example is the iron site on hemoglobin that binds oxygen in your red blood cells. I would guess that bacteria can do the substitution themselves, which is to say they should be able to build their own enzymes from the elemental forms of the required minerals rather than necessarily requiring the amino group preformed. The point I am trying to make is mineral deficiencies might kill off various strains of gut bacteria.

Overall I think this line of research is very interesting and likely to provide many interesting results. This might, for example, end up being a very strong argument against the prophylactic employment of antibiotics. At a minimum, patients should be prescribed probiotic cultures after their antibiotic treatments, and, oh yeah, those probiotics should actually be, you know, alive when ingested.

A useful research project would be a large-scale longitudinal study (tens of thousands of patients over 10 - 15 years), where patients' gut bacterial colonies are sampled at regular intervals and the patients are monitored for the development of various diseases. The initial states of gut flora, if they remain consistent, may produce correlations for the relative risks of various diseases. If the composition changes, the natural question is if any new diseases presented at the same time. The US National Institute for Health has instituted a survey program to determine the genomes of gut flora, the Human Microbiome Program, which is an important first step.

I started taking a Lactobacillus and Bifidobacterium probiotic a couple of weeks ago as a trial. I did notice changes in my stool almost immediately; for the sake of brevity I will spare you the details. Bacterial cultures, like fish oil, should be stored in the refrigerator but unlike fish oil bacteria don't withstand freezing too well.

Clarifying Butter (i.e. Ghee) Guide

2009-11-16T11:01:00.001-07:00

Mmm... butter, one of the tastiest of all fats. It also happens to be one of the most nutritious forms of dietary fat, containing the fat soluble vitamins A and D in their animal usable forms. It is also a good source of vitamin K₂, which regulates calcium metabolism; K₂ has become quite rare in our modern diet with its lack of fermented foods. Unfortunately, butter does contain some milk solids, so if you are gluten intolerant you may also be intolerant of the α-casein that makes up some 80 % of cow milk proteins. It also contains a little bit of lactose, which might make someone with lactose intolerance hurl. What to do? Why remove the milk solids of course. This process is called clarification and can easily be done on the stove top. The finished produce is often called Ghee, as it was once a staple of Indian cooking.

An additional advantage to clarifying butter is that it does not brown or burn nearly as easily so cooking with it at high temperatures is safer. Traditionally ghee is often flavoured with cinnamon or cloves. Incidentally cinnamon is a folk-method for treating diabetes; it has an insulin-like effect in addition to being high in chromium.

I typically clarify two pounds of butter at a time. Since the volume of the butter will be reduced by about 1/4 (primarily water and the filtered milk solids) this yields about 750 mL of high quality cooking fat. You'll want the following ingredients and apparatus:

2 lbs. butter (cultured butter will taste better)
optional: wholes cloves and cinnamon stick
sauce pan
ladle
thermometer, digital w/ alarm
strainer
elastic band (like the type broccoli stalks come with)
terrycloth or cheesecloth

First start by melting the butter in the pan on low. As it melts to cover the bottom of the pan you can turn it up to medium and stick your thermometer into the oil. Set the alarm to 110 °C (230 °F). You don't want to use high heat here, as there's only a limited amount of water in the butter so it's mostly just a matter of time for the oil to heat up.

When water evaporates it takes away an enormous amount of heat, so the temperature of the ghee will stall a bit at or just above 100 °C (212 °F). At this point, the butter will separate into its three constituents: the milk solids, which will settle on the bottom, the golden-coloured oil itself, and a layer of foam on the top.

The foam does not contain casein, but it is unsightly and we want to get rid of it with our strainer. Just skim around the top, and then wash the strainer off with hot water. After 2-3 skims, you should have a cleaner looking product.

After cleaning off the foam you are essentially just boiling away the water content of the butter. Honestly if you know what you're doing and watch the butter carefully you don't need the thermometer. As the oil heats up, the bubbles will get smaller and smaller. When the oil stops bubbling, that means all the water has evaporated and the temperature of the oil will start to rise very quickly. When or if the milk solids at the bottom of the pan start to turn brown, remove the pan from the heat immediately. I generally wait until 125 °C (257 °F) to finish heating.

At this point it's time to transfer the clarified butter into your jar. I use terrycloth instead of cheese cloth for a few reasons. One, it is far cheaper and easier to find. It's even reusable, and it seems to do a better job of filtering the milk solids than cheesecloth. I do wash it beforehand. The elastic is wrapped around the base of the strainer to hold the filter in place.

That's it! Now just cap your jar and clean up. The hot ghee will be transparent and look a fair bit like thick urine. If any milk solids did make it through the filter process, they will settle on the bottom. As it cools to room temperature, it will become more solid and turn a pale yellow colour.

Ghee is shelf-stable although I would store it in a cupboard away from light. It can be refrigerated but it becomes very hard at colder temperatures and impossible to get out of the jar with a spoon.

If you can't afford high-quality grass-fed organic butter (I certainly can't), you may want to consider adding vitamins D₃ and/or K₂ if you can buy them in drop form. Add them to the finished ghee in the jar and stir.

Vegetarians who Eat Meat

2009-11-09T14:31:00.002-07:00

I made a comment on my last post about the paleolithic principle on the notion of, "vegetarians who eat meat." I had to laugh when I read this post on TheAtlantic.com by Marion Nestle, "Are Vegetarian Diets Healthy?" A quote that illustrates the funny:

But before getting into all this, there is the pesky problem of definition. What, exactly, is a vegetarian? As it happens, people who call themselves vegetarians eat many kinds of diets. The least restrictive vegetarians do not eat beef but occasionally eat pork or lamb. Next come the groups that eat no red meats, or restrict poultry, dairy, fish, or eggs. The most restrictive are vegans who eat no foods of animal origin at all.

It's as if everyone claims CAFO pork is better for you than grass-fed beef, it must be true...

I've covered this briefly in the past. Vegetarians who eat fish had lower overall incidence levels of cancers than vanilla vegetarians, and both were better than the British Standard Diet eaters. Once again, maybe it isn't meat that's the problem per say, but that people who don't eat it have a better relationship to their food (on average) than people who do (on average). What, exactly, does a vegetarian eat at a fast food restaurant? Do they eat at fast food restaurants? Or do they bring a bag lunch to eat most work days?

Your, "food culture of one," matters. Eat that which doesn't make you sick.

The Paleolithic Principle

2009-11-01T08:34:00.006-07:00

I would like to share an overview of how and what I eat, and why. Rather than list individual food items, I will discuss the approach in general terms. I won't really be rigorously supporting many of my statements since that would require an entire book or more worth of writing. I will try to keep this brief and information dense.

I structure my nutritional philosophy around the notion of the Paleolithic Principle. The principle is that the human animal has been around and eating a relatively consistent diet for a couple of million years with Homo Sapiens being around for almost 100k years. It was only really with the introduction of the neolithic age that technology brought new foodstuffs to consume such as dairy, grains, and the other modern cultivars of plants that we eat. The paleolithic principle states that we have not fully adapted to these new types of foods and hence they may be harmful to our health, on a case by case basis.

These new sources of food were introduced roughly 5000 - 7000 years ago, which is perhaps some 300 generations worth of time. Humans, being long-lived, evolve quite slowly. Humans, being highly social sentient apex predators, also don't necessarily experience the same degree of natural selection as other species. The question is then, just how well adapted are we to these neolithic food groups?

We know for a fact that food tolerances have an ethnic bias. We know that the closer one's ancestors hailed from Mesopotamia the less likely they are to be intolerant to wheat gluten. Similarly, Asians are far more likely to be lactose intolerant than Europeans. Thus, clearly, only certain segments of the human population have adjusted to each particular Neolithic foodstuff. These are established facts, and they provide a basis for the paleo principle as a reasonable hypothesis.

If one has an ethnic background that strongly identifies with a particular ethnic diet then you might be best off following it since you're probably selected for it. This doesn't always work well however, especially in the immigrant nations such as the USA and Canada, where there has been a great deal of mixing in ethnic groups. Personally, I'm a mix of Polish-Romanian jew, Italian, French, Norwegian, Scottish, Austrian, and English, with a few other nationalities thrown in for fun. If I were to follow an ethnic diet, which of the ten or so should I pick? Almost all of the neolithic food groups give me some trouble. Perhaps I'm simply lacking in intestinal fortitude.

The largest quantity of pharmaceuticals that one ingests by far is in the form of foodstuffs. Plants especially contain an enormous number chemical compounds, not all of which are broken down before they cross the gut-blood barrier. For whatever reason, the gut-blood barrier and the associated bacterial biofilm has broken down more commonly in modern man.

Of course, even foodstuffs that we have been (slowly) adapting to over 5000 - 7000 years have changed a great deal. For example, the heavy fertilization of dwarf wheat strains has resulted in higher protein yields but that protein predominantly comes in the form of increased gluten content. So when people scratch their heads about the increased incidence of celiac and other gluten related autoimmune disorders, it may just be that the wheat is changing rather than the people, n'est-ce pas? Similarly ever compared a wild strawberry to a super-fertilized all-season Californian monstrosity? We have started supplementing our diet with artificial food additives, such as mono-sodium glutamate (MSG), which only further complicates our understanding of nutrition.

Modern farming practices, cultivars of plants, and breeds of animals sacrifice micro-nutrient content for economy in the form of macro-nutrient content. In some cases, you don't even get more macronutrient, but just more water content for the check-out scale. Thus you have the paradox of a person who is obese yet simultaneously starving thanks to a diet of soda pop and it comes about due to the imbalance in the ratio of micro-nutrients to macro-nutrients in the foods we eat. This is the tyranny of the middles aisles in the supermarket.

Now, the paleolithic principle is sort of like using a sledgehammer to pound in a finishing nail (HT: Chris). It works, it works quite well actually, but it is an excessive means to the task. I don't ascribe to the fairy tale view that everyone was engaged in happy-fun-time back before the introduction of agriculture but there's little doubt that hunter-gatherers were physically far more impressive animals than the more numerous agriculturalists and pastoralists that out-competed them.

It's clear to me that industrialization and technology has had a number of negative consequences to human health which we call the "diseases of civilization." The most obvious of these are heart disease, diabetes and obesity (including metabolic syndrome), but they also include autoimmune disorders (which are far more common than is generally recognized) as well as many neurological disorders. I don't think it has to be this way, but there have been some very wrong-headed paths taken in the field of nutrition over the past fifty-odd years.

From an evolutionary perspective, the more recently a particular foodstuff was introduced, the more likely it is to cause distress. This implies that refined oils and large quantities of fructose, both of which were entirely absent in the 1800s, are two of the more obvious places to eliminate and cut-back in order to restore the good health nature intended us to have.

If I were to sum up a reasonably brief list on what to do and what not to do, this would be it:

Control appetite hormones like gherlin by eating regular, satiating meals. By satiating I mean protein, fat, and fibre. Try to avoid snacking.
Restrict fructose and alcohol consumption to reasonable levels, day-to-day. 20 g/day of both combined would be a very healthful level, 50 g/day is I think an upper bound for people with healthy livers.
Eliminate industrial, refined oils, particularly refined polyunsaturates such as soy and canola oil. Go for fresh and high quality fats, in particular clarified butter, extra-virgin coconut oil, extra-virgin olive oil, and the fats from animals fed their native diet. Unstable oils should be stored in the refrigerator or freezer to prevent them from going rancid, e.g. Omega-3 fish oil capsules. Most industrial oils are deodorized to prevent you from smelling when they go bad.
Eat more than just muscle meat from an animal. Have you eaten liver pate or roasted heart lately? Bone broth?
Fast occasionally for approximately 24-hours to give your liver a break and restore insulin sensitivity. Many religious groups noted for their good health (i.e. Seventh-day Adventists, Mormons, and the Greek-Orthodox of Crete and Corfu) regularly fast — is the the shared common trait. Fasting and starving are not the same thing, don't conflate the two.
Go on elimination dietary trials of the common food allergies: wheat (including barley and rye), cow dairy, legumes, especially soy and peanuts, tree nuts, eggs, fish, and shellfish. Test assays may be insufficient to recognize many of the idiopathic problems (i.e. autoimmunity, neurological disorders) that these types of food may induce. It took me six months wheat-free to get better.
Supplement with Vitamin D, on the order of 1000 IU/12 kg of body mass per day. Consider that the recommended doses for infants are 400 IU/day, so if you mass ten-times that of an infant, you need ten-times as much vitamin D; recommended adult doses are a joke. Also consider that you produce about 10,000 IU/ 30 minutes in full-sun. Vitamin D is not a vitamin, it is the precursor material to most of the steroid hormones in your body. When the endocrine (hormone) system has adequate signaling compounds, the whole body works better.

I do not eat much in the way of carbohydrates primarily since wheat and dairy are off-limits to me but even more so was the realization that foodstuffs that are good sources of glucose are also bereft of micro-nutrients. I.e. they are empty calories. You know how some people drink socially? I eat grains socially (with the notable exception of wheat, which I find incredibly destructive to my body). This said I don't believe glucose is inherently a problem and I do carb-load from time to time.

You may have noticed that I haven't talked about exercise at all, and that's because I think it is relatively unimportant. If you apply the 80/20 rule to how well you feel, I think perhaps 80 % of your wellness comes from diet, 15 % from adequate restful sleep, and perhaps 5 % from physical activity. Trying to lose body fat from exercise is a fool's errand and more than likely will result in over-training and the associated chronic injuries. While I personally do get a lot of physical activity, it's all for fun. My current hobby is whitewater kayaking, so any physical training I do is oriented towards improving my performance in that regime rather than building bulging biceps. I don't bother lifting weights in the gym since I find it quite dull. The fact of the matter is I got healthy through diet first and only then started exercising more.

Now, you may have noticed me talk about autoimmunity a lot and that is because I think it plays a key role in the diseases of civilization. Autoimmunity is simply the case in which the immune system, which is responsible for both healing and repealing foreign invaders, starts attacking the tissues of its host body. Autoimmunity has a genetic component, but something needs to trigger it. Examples are viral or bacterial infections, or dietary allergies. Celiac is one type of autoimmune disorder, type 1 diabetes is another.

If the diet is introducing strange, novel foreign bodies into the gut and the gut is compromised, they will penetrate into the circulatory system. The immune system sees these foreign bodies and goes berserk trying to hunt them all down and destroy them. Then, four to six hours later, you eat another meal and the cycle repeats. The solution is to remove the stimulus, i.e. fix the diet.

Any sort of food allergy or intolerance is likely to result in the immune system being depressed. The immune system only has a finite capacity for fighting infection, and if you're making it waste its time chasing gluten peptides or whatever, it is not going to be so strong at fighting off the latest pathogen. Similarly if you are not providing the immune system with enough micro-nutrients to operate at full capacity you will not only get sick more often, but you will also heal more slowly.

If I could sum up my nutritional philosophy in one sentence it would be:

Don't eat things that cause your immune system to run around like it has a hole in its head.

A touch different from Michael Pollan, but I digress.

Wanted: Muse

2009-10-26T23:20:00.001-06:00

I'm trying to write a post and an article, but words are just not coming onto the page. Isn't it funny how sometimes you've just "got it" and sometimes you have absolutely nothing?

Breakthough in Flow Batteries?

2009-10-14T10:24:00.003-06:00

So there's been a little Google explosion on the subject of flow batteries recently, with a German group claiming a breakthrough. From the press release,

Until now, however, redox flow batteries have had the disadvantage of storing significantly less energy than lithium-ion batteries. The vehicles would only be able to cover about a quarter of the normal distance – around 25 kilometers – which means the driver would have to recharge the batteries four times as often. “We can now increase the mileage four or fivefold, to approximately that of lithium-ion batteries,” Noack enthuses.

Mmm... vague, yes? As anyone who has been following the alternative energy scene for any length of time knows, the bigger the claim and the fewer facts behind it, the more likely it is to be BS. As always, it pays to be skeptical rather than credulous.

If you aren't familiar with the technology of flow batteries, I suggest you buck up to Wikipedia and take a read. The strong point of flow batteries has always been that the power and energy storage characteristics are decoupled: the power is a function of the size of exchange membrane, while the energy storage is determined by the volume of the storage tanks. In this fashion, they are a lot like fuel cells except that they are reversible. However, the energy density (as a function of weight or volume) has never been terribly impressive, lying around that of lead acid batteries.

The engineer who is quoted in the story, Noack, appears to be involved with the design of the exchange membrane and I can't see the mechanical bits resulting in a 4 - 5 fold improvement in energy density. I found a paper he wrote here comparing the various known chemistries applied to a new membrane stack design. There must have been some new chemistry developed, either that or there's smoke and no fire here. The article does mention collaboration with the University of Applied Sciences, Ostphalia [sic], but I can't find anything pertinent on the university's web site.

The previous king of the various redox flow battery chemistries is the Vanadium redox battery. It can, in general, obtain a 75 % round-trip efficiency which is fairly decent, being roughly in-between Li-ion batteries and Nickel-metal hydride batteries. The Achilles heel has always been the chicken and egg problem of the cost of Vanadium. Vanadium is not a particularly rare element, but it isn't mined in large quantities due to lack of demand and hence it is quite expensive. A single utility scale redox battery would consume a significant portion of the world's annual Vanadium production. Thus the conundrum, if no one can afford to buy a Vanadium redox battery, you'll never generate enough demand for Vanadium to open up new mines and drive the price down. The best hope, I always thought, was for one of the Vanadium-contaminated oil deposits of the world to be developed and glut the world Vanadium market.

As far as I know the intellectual property behind the Vanadium redox battery was held by VRB Power Systems but they went bankrupt earlier this year. They seem to have been acquired by a Chinese firm, Prudent Energy. It's probably worthwhile that the dollar numbers for Vanadium redox batteries didn't work out, even way back in 2005 when I last looked at it.

The Chronic Infection Theory of Heart Disease

2009-08-28T13:06:00.003-06:00

Introduction

Heart disease, or more specifically atherosclerosis, is a chronic disease whereby cardiac arteries become partially occluded by the growth of plaques. Narrowed arteries are more likely to trap dislodged blood clots, resulting in blood supply being cut off to a portion of the heart, resulting in oxygen depletion of the cardiac muscle tissue and eventually myocardial infarction or heart attack.

Contrary to common wisdom, dietary fat does not deposit on the arterial wall and "clog your arteries;" plaques grow inside the arterial cell wall and consist of a mix of the smooth muscle cells that naturally line the interior lining of the artery and immune-system cells such as macrophages and lymphocytes. Macrophages, or white blood cells, are the large, amoeba-like cells that form the last line of defense for the immune system. This mix of cells are called foam cells. Foam cells tend become bloated by absorbing large amounts of cholesterol from the blood stream and they form a cyst or lesion which compresses the arterial wall, reducing the effective diameter.

By way of background, there are three times of muscle in the body: cardiac, skeletal (meat muscle, like your bicep), and smooth muscle (such as your scalp or vital organs). Smooth muscle is quite a bit different from the other types in that its cytoskeleton has no deterministic, regular structure. Rather, it just consists of a chaotic jumble of actin filaments. Unlike the other two types, smooth muscle is not normally controlled by the electronic action potentials of the nervous system; rather, it is controlled by the much slower chemical hormonal system.

With time, atherosclerotic lesions may harden by absorbing calcium from the blood which makes the artery stiffer and tends to result in high blood pressure. This is not unlike how bone tissue is formed by the mineralization of connective tissue, which in turn suggests some sort of hormone dysfunction is in play. Hardened arteries are considered more hazardous than pliable yet still narrow arteries. The likely reason for this is that a narrowed yet pliable artery can distend under pressure to allow a blood clot through, while a calcified artery cannot.

Thus we have three criteria for heart attacks (with some simplification):

The wall of the cardiac artery has to be sufficiently narrowed so that,
A dislodged blood clot gets stuck in it, and/or an atherosclerotic lesion ruptures (in the majority of heart attacks anyway), and
The arterial wall is too stiff to allow the build-up of pressure caused by the obstruction to allow the clot through, resulting in down-stream oxygen deficiency and eventually cell death.

To reduce heart attacks, you can attack any of these three processes. Take the Masai tribesmen of Tanzania: they have a great deal of atherosclerosis thanks to their milk-based diet, but they don't necessarily suffer heart attacks, likely due to their adequate intake of vitamin K₂.

I want to talk about the first requisite, atherosclerosis. The question is of course, what causes immune system bodies to form colonies inside the lining of one's arteries? There are two basic possibilities: auto-immune disorder, where the immune system recognizes legitimate tissue as foreign, or actual foreign bodies, such as chronic bacterial or viral infection of the blood vessel. Or both.

Enter Chlamydia pneumoniae, bacterium

The idea that atherosclerosis might be caused by chronic infection of the lining of blood vessels is not a new one. In 1999, the American Heart Journal devoted a supplementary issue to the topic. It is, essentially, an alternative theory for heart disease as compared to the diet-heart hypothesis, whereby diet modifies serum cholesterol levels which in turn causes heart disease by some unknown mechanism. As it contraindicates the standard lipid model, it is considered controversial. The first potential pathogen candidate was cytomegalovirus (aka herpes) but it turned out to be a bust.

Further research suggested a better candidate. Chlamydia pneumoniae (aka Chlamyophila pneunomiae) is the bacterium most commonly associated with heart disease in the literature. As the name suggests, it is one of the sources of pneumonia and other respiratory infections. It has also been associated with Alzheimer's and asthma. It is a relatively recently discovered pathogen (in that the diet-heart hypothesis was formulated before anyone knew it existed), and its responsibility for respiratory infection was only discovered in 1986 (Grayson etl al., 1986). The association with heart disease was made very quickly (Saikku et al., 1988), since the hunt for a potential atherosclerotic pathogen had been underway since the early 1980s.

Bellard et al. (2003) lay down the case for C. pneumonaie succinctly,

Exposure to Chlamydia pneumoniae is extremely common, and respiratory infections occur repeatedly among most people. Strong associations exist between C. pneumoniae infection and atherosclerosis as demonstrated by: (i) sero-epidemiological studies showing that patients with cardiovascular disease have higher titres of anti-C. pneumoniae antibodies compared with control patients; (ii) detection of the organism within atherosclerotic lesions, but not in adjacent normal tissue by immunohistochemistry, polymerase chain reaction and electron microscopy and by culturing the organism from lesions; and (iii) showing that C. pneumoniae can either initiate lesion development or cause exacerbation of lesions in rabbit and mouse animal models respectively.

This list is not exhaustive, and it does not note probably the most important point: C. pneumoniae can create foam cells in vitro (i.e. in a Petri dish). C. pneunomiae has been shown to infect the constituent cells in foam colonies (i.e. macrophages and smooth muscle) (Fryer et al., 1997), inhibit the mechanism whereby cholesterol (LDL) is relinquished (Kalayoglu, 1999), and oxidize low-density lipoprotein (LDL) via releasing heat shock proteins (Kol et al., 1998). More on this later.

The physical presence of C. pneunomiae in atherosclerotic lesions has, as previously mentioned, been detected by a wide variety of methods. It's also highly prevalent. Of many studies that have found C. pneumoniae in foam colonies, (Muhlestein et al., 1996) is probably the most solid. From a population of 90 patients, they found evidence of C. Pneumoniae in 79 % of atherosclerotic plaques, but only 1 of 24 control biopsies.

A basic question then is how does one particular type of bacteria manage to not only evade the immune system, but distort its response in order to cause great harm to the host? (Belland et al., 2003) explore the mechanism,

Chlamydial growth is biphasic, consisting of two alternating functional and morphological forms (Fig. 1). The elementary body (EB) is the metabolically inert, infectious form of the organism that is capable of transient extracellular survival. EBs bind to as yet undefined host cell receptors, are internalized via a pathogen-specified process and are detectable within a membrane-bound vesicle immediately after entry. This vesicle is capable of interacting with post-Golgi secretory vesicles in ways that allow for the incorporation of host phospholipids [RM: phospholipids are cell membranes, i.e. camouflage] (Hackstadt et al., 1996; 1997). Chlamydiae also block intracellular host cell responses, such as fusion of the pathogen-containing endosome with lysosomes, and thus avoid host cell factors that would be detrimental to intracellular survival. Soon after entry, chlamydiae differentiate from infectious EB to the intracellular replicative form of the organism, referred to as the reticulate body or RB. This differentiation, which is dramatic in terms of altered chlamydial morphology, must reflect an orchestrated sequence of differential gene expression. Transformation of EB to RB results in loss of the disulphide cross-linking of the outer membrane complex, decondensation of the genome and initiation of DNA, RNA and protein synthesis. RB multiplication results in the formation of an intracellular microcolony (termed the inclusion) of chlamydiae.

Ok so that's a wordy quote, but to sum it up in one word it is mimicry. A big area of research in bio-nanotechnology is the development of phospholipid coatings on implanted medical devices to prevent the immune system from recognizing them as foreign and attacking them. This technique is known as, "stealth technology." Here we have an example of an organism that has evolved this technique. <acerbic>But don't you dare eat any eggs, they have cholesterol in them</acerbic>.

It's not clear if C. pneumoniae causes all atherosclerosis but I do believe it causes a majority of such. Another potential source of plaque-forming bacteria is Helicobacter pylori, which among other things, is thought to be responsible for ulcers. Unlike C. pneumoniae, which enters through the lungs, H. pylori typically lives in the gut. A study by Mayr et al. (2000) found an association between H. pylori antibodies and cardiovascular disease, but only in the low status (i.e. poor) individuals in their population. This study was conducted in Austria, so one wonders what might poor Austrians be eating that would cause them to suffer H. pylori infections?

The same paper also found odds ratios for: IgA type antibodies to the C. pneumoniae bacteria, elevated C-reactive protein levels in the blood, and (clinical) chronic respiratory infection. Now, odds ratio is a funny, non-intuitive statistic, but we can directly compare it to odds ratios found in other studies.

Table 1: Odds ratios for various diseases of affluence.

Description	Odds Ratio
Top quartile LDL cholesterol developing coronary artery disease within six years. (El Harchaoui et al., 2007)	1.73
Any one of: IgA antibodies to C. Pneumoniae. Elevated C-reactive protein levels. Clinical chronic respiratory infection.	1.5
Two of above.	4.33
Three of above.	10.28
Smokers developing Lung Cancer, versus non-smokers (Doll & Hill, 1956)	12.8

As you can see, three out of three is quite a strong association, far stronger than the cholesterol testing that is the most common method of screening for heart disease risk in medicine today. It is actually getting close to that of smoking and lung cancer, which is the gold-standard for causation. If you break it down individually, the strongest of the three criteria is chronic respiratory infection (OR of 3.8), followed by C-reactive protein (OR of 2.4). Since C. Pneumoniae antibodies has the poorest odds-ratio, while the chronic conditions are much higher, we can probably surmise that being infected once isn't going to cause atherosclerosis, in the same sense that over-drinking once is not going to cause fatty liver disease. Heart disease is a chronic condition, caused by chronically applied vectors (i.e. diet and environment). For the same reason, antibiotics were found to be ineffective in treating atherosclerosis: they are effective for acute infection, but in the long run they cause as many problems as they solve, since many of the bacteria in our bodies are beneficial and help out-compete teh nasties [sic].

Heat Shock Proteins

Another issue, that I eluded to above, is what exactly is causing inflammation in this case? Medicine has identified oxidized-LDL as a major danger factor, but is this a cause or just a symptom?

One potential candidate is a class of proteins that are produced by cells under stress, collectively known as heat shock proteins. The name is not well chosen, heat shock proteins should be termed temperature stress proteins. They are produced by cells that are under elevated temperatures (or many other forms of environmental stress) and they protect the other functional machinery of the cell from future elevated temperatures. They are considered to be a part of the general inflammation response of the body, although they tend to operate on a small, single-cell (i.e. autocrine) scale.

Foam cell colonies produce one particular type of heat shock protein, HSP60, in large amounts.
This particular heat shock protein is usually associated with mitochondria, the energy factories of cells, but it's also known to interfere with apoptosis, or programmed cell death. Apoptosis is the way in which the body normally disposes of broken or old cells. Elevated levels of HSP60 prevent apoptosis from occurring (Gupta and Knowlton, 2005).

One study on 1003 Chinese men found an odds ratio of 2.3 for atherosclerosis by simply being in the top half of the population for HSP60 levels in the blood (Zhang et al., 2008, full-text link on Pubmed is broken and is available here). Those in the top quartile for HSP60 levels had an odds ratio of 4.87, which higher yet than the range usually seen for c-reactive protein, which is the standard marker for inflammation.

The high odds ratio with c-reactive protein has been seen as one of the supporting features for the slowly evolving, mainstream view that inflammation and not blood lipids are responsible for heart disease. But is inflammation the cause or symptom again, and what causes localized inflammation of the blood cell wall anyway? The fact that arterial foam cells produce heat shock proteins and a bevy of other inflammatory markers in quantity suggests that atherosclerosis causes inflammation, rather than the other way around. Indeed, studies have claimed that the chlamydial heat shock protein 60 (cHsp60) oxidizes LDL particles in a test tube (Kalayoglu et al., 1999). This is big deal, since the actual mechanism whereby LDL oxidizes isn't known. For example, see Steinberg, 1997:

First, patientsand animals totally lacking the LDL receptor nevertheless accumulatecholesterol in foam cells much the same way as do patients andanimals with normal LDL receptors; second, the two cell typesin lesions that give rise to cholesterol-laden foam cells (themonocyte/ macrophage and the smooth muscle cell) do not accumulatecholesterol in vitro even in the presence of very high concentrationsof native LDL (3,4). This paradox could be resolved ifcirculating LDL underwent some form of modification and if themodified form, rather than native LDL itself, then served as theligand for delivery of cholesterol to developing foam cells.

There are no paradoxes in medicine, just an inadequate understanding of nature. That, and a heaping load of bias. If it is the heat-shock proteins that are causing much of the trouble, then we have some idea as to why foam cells are sustained by the body. The heat shock proteins produced by these bacteria closely mimic the same heat shock protein produced by the arterial wall (Hsp60). Heat shock proteins are one of the basic lego blocks of living cells, and there's not a great deal of variation between those HSPs produced by highly evolved human cells compared to say, yeast. The fact that HSP60 inhibits programmed cell death is another fascinating thread to pull on. Another possibility that occurs to me is that real bacterial infection may be transformed over a long time into an auto-immune disorder, even if the original bacteria have died off. More research is needed to assess just what the half-life of C. pneumoniae is in foam cell colonies.

Known correlations with heart disease

So how are these bacteria getting through the mucous tissues and into the blood stream? The correlation between smoking and heart disease is explained nicely by this hypothesis. Smoking compromises the lungs, leading to C. pneumonia or some other form of infection, which in turn results in atherosclerosis.

One might expect then that other chronic conditions that break down the walls of the mucous membrane/exterior environment barrier could also lead to atherosclerosis: dietary components that cause leaky gut, periodontal disease, and possibly fungal infections. Alternatively, substances that suppress immune system function could be associated with cardiovascular disease.

Other chronic diseases that results in a breakdown of the bloodstream-mucus-environment barrier should also show increased rates of heart disease. The two most obvious choices to me are celiac disease (where wheat gluten destroys the lining of the intestines) and periodontal disease (of the gums in the mouth). For celiac disease, there doesn't seem to have been any research on the topic. Of course, it would be ethically impossible in a clinical setting to find undiagnosed celiac patients and follow them to assess heart disease. Once celiacs are diagnosed, their treatment is straight-forward (i.e. don't eat wheat or casein). However, perio is more difficult to resolve and the results on periodontal disease seem to be consistent, with perio causing a small (relative risk 1.24-1.34) yet consistent and significant increase in heart disease average over many studies (Cronin, 2009).

Similarly, substances or deficiency of certain materials in the diet that suppress or deform the immune system response could have an impact on heart disease. The most obvious would be insufficient vitamin D intake.

Conclusion

When it comes to the diseases of Western civilization/diet, we always must ask the question, what is the mechanism? A top-down approach is simply insufficient because separating correlation and causation in living organisms is so difficult and one is consistently tempted to simplify the details rather than break them down into first principles. Hence the enormous failure of pursuing cholesterol as a cause of heart disease, instead of recognizing it as a symptom. The false path of the cholesterol hypothesis has to rank of one of the greatest scientific blunders of all time and is indirectly responsible for the premature deaths of millions.

On the other hand, the chronic infection theory of heart disease is internally consistent with the data that are available to us. We know that C. pneumoniae is a common form of respiratory infection, and that once in the bloodstream it can infect smooth muscle and macrophage cells both in vivo and in vitro. We know that C. pneumoniae can disrupt the cholesterol metabolism of foam cell colonies in vitro. The chameleon nature of C. pneumoniae illustrates how foam colonies can be be persistent in the face of the immune system and morph an acute infection into a chronic condition. I just don't see any gaping holes in the theory. We still need to explain why C. pneumoniae (and other bacteria like H. pylori) affects some individuals and not others, but the how is reasonably explained and justified.

Author's note: I started writing this post on May 13th, 2009.

Feynman Lectures on the Web

2009-08-26T22:25:00.002-06:00

Bill Gates recently purchased the rights to a series of lectures by renowned physicist and teacher Richard Feynman. Feynman was a nobel winner for and essentially the father of the field of quantum electrodynamics, and also did a lot of work on superfluidity of liquid helium. The breadth of his contributions has to mark him as one of the top physicists of all time, possibly top-five, certainly top-ten.

Feynman proves the adage that it is not science that is staid and boring, but rather scientists are staid and boring. Anyone who has written journal publications will know what I'm talking about here.

Project Tuva: The Messanger Series

You will need to download and install (Firefox users: manual installation) a Microsoft plug-in to view them but they are really a great resource. In short, they are a perfect way for someone who has only a cursory understanding of science and wants to know more, yet doesn't know where to start. For experts, they are still useful to get your mind out of the minor details that dominate scientific discourse today and thinking about the big picture once again.

My favourite lecture by far is #6 on the dual wave-particle nature of fundamental particles like photons and electrons. This lecture is very close to one of my thesis topics, on the double slit experiment. Interestingly, around thirty minutes in Feynman becomes partially incorrect as he talks about the coherent and incoherent modes as in reality, there is only partial coherence.

Har har har... (you have to be a physicist).

For very small angle scattering, i.e. ΔE/E_o is very small, the interference is less but still present. To put numbers on these, we're talking about ΔE=1-20 eV energy loss compared to E_o=300,000 eV in the denominator, or angles less than 0.004 °.

Vacation

2009-07-22T10:25:00.001-06:00

I'm going to Richmond, VA for a conference followed by vacation in Ottawa, ON until the 7th of August. I might crank out a post in the in-term, although I wouldn't bet on it.

Toodles.

Observational Study on "Cancer incidence in British vegetarians"

2009-07-08T12:19:00.007-06:00

Key et al. reported in the British Journal of Cancer a large observational study that compared cancer incidence between groups based on diet. This article claims to be free access to the public. The corporate media love to report on research like this because they find it simple to tease good headlines out of them. Unfortunately, the closer you look at observational studies, the less sure of anything you end up being.

The study split 61566 Britons into three groups, 'meat-eating' (N = 32403), 'fish-eating vegetarians' (N = 8562), and 'vegetarian' (N=20601). Unfortunately, the study did not split up lacto-ovo vegetarians from vegans, as that may have been interesting due to the removal of another food group in the form of dairy.

The 'meat eating' group could be better described as the 'standard British diet' group. There are substantial differences in the approach to food between vegetarians and the stereotypical general population. This is particularly evident in the degree of industrial, processed food consumed although when I go to organic food markets I still see plenty of crap in the middle aisles.

There were, of course, differences between the three groups that were not dietary:

The mean age at recruitment was lower in the fish eaters and vegetarians than in the meat eaters. Smoking rates were low overall, with only 14.4% of meat eaters, 11.2% of fish eaters and 11.4% of vegetarians reporting that they were smokers at the time of recruitment. The median BMI was 1.5 kg m^-2 lower in vegetarians than in meat eaters, and the median alcohol consumption was 1.0 g per day lower in vegetarians than in meat eaters. Fish eaters had similar mean BMI to the vegetarians and had similar alcohol consumption to the meat eaters. The proportions of men and women who reported a relatively high level of physical activity were higher among fish eaters and vegetarians than among meat eaters. The proportion of women who were nulliparous at recruitment was higher among fish eaters and vegetarians than among meat eaters, and the proportion of women who had ever used oral contraceptives was lower among fish eaters and vegetarians than among meat eaters.

The authors claim to have corrected for these factors in their results for cancer risk factors, and that an uncorrected analysis had similar results to the corrected one (i.e. that the differences did not impact the results).

Table 1: Relative risks of cancer for various forms, RR = 1.0 for the 'Meat Eaters' group.

Selected Major Cancer Types	Fish Eaters’ Relative Risk to Meat Eaters	Vegetarians’ Relative Risk to Meat Eaters
Upper GI tract	0.44 (0.16–1.25)	0.81 (0.45–1.46)
Stomach	0.29 (0.07–1.20)	0.36 (0.16–0.78)
Colorectum	0.77 (0.53–1.13)	1.12 (0.87–1.44)
Lung	0.59 (0.29–1.23)	1.11 (0.75–1.65)
Melanoma	0.90 (0.55–1.47)	0.89 (0.61–1.29)
Female breast	1.05 (0.86–1.28)	0.91 (0.77–1.08)
Prostate	0.57 (0.33–0.99)	0.87 (0.64–1.18)
Lymphatic	0.85 (0.56–1.29)	0.55 (0.39–0.78)
Cervix	2.05 (0.91–4.63)	2.08 (1.05–4.12)
Overall	0.82 (0.73–0.93)	0.88 (0.81–0.96)

The results were statistically significant only for stomach, lymphatic, and cervical cancers, and the overall results were also significant. The uptick in cervical cancer is interesting, but not particularly important given how easily it can be avoided through vaccination. What's interesting is that the fish-eating vegetarians appear to have lower risk factors than the pure vegetarians.

It's a little hard to make the claim that meat per-say is the causative factor when you take vegetarians and feed them fish and their cancer incidence drops. In the discussion, the authors' implication focuses on nitrates and other work has shown that heterocyclic amines produced by charing/burning food (not just meat) can be hazardous. Alternatively it could be something like deep frying food in vegetable oil, since its polyunsaturated content is so easily oxidized in such an environment. Could vegetarians be buying more organic food and ingesting lower levels of pesticides? Etc. To paraphrase Simon Pegg, identifying the causative factor is like trying to hit the bull-eye on a dart-board that is mounted on a F1 car, while blind-folded, and riding a horse.

This is the drawback of observational studies: you can't make any definitive conclusions from it. At best, it can act as a guide, but it's sort of like hiking in the mountains: do you follow that old blaze when the trail forks or do you try and orient yourself? The drops in cancer rates (-18 % for fish-eaters, -12 % for vegetarians) are no smoking gun. The drop in stomach cancer is impressive. By way of comparison, the rate of lung cancer in non-smokers is roughly 3 % (i.e. RR = 0.03) compared to heavy smokers.

Ontario Cancels New Nuclear Power Plant Plans

2009-06-29T12:02:00.002-06:00

Via Karen Howlett at The Globe and Mail, we learn that Ontario has suspended its plans to build some new nuclear power plants. The leading bid was from AECL. There have been rumblings that Atomic Energy Canada Ltd., which is a crown corporation, may be privatized by the federal government. This sort of leaking about the corporation's future probably isn't helping them land any sales. I suspect part of these funds will (have to) be restored to refurbish the existing reactors since they are going to need it to continue operating in the future. Ontario is about 50 % nuke powered; the only other nuclear plant in Canada is located in New Brunswick.

My long-standing belief is that civilization will need to build another generation of nuclear power plants to supply base-load electrical power. I've also long felt that nuclear power is more expensive, notwithstanding subsidies, than renewable sources like solar or wind will become. Initially the renewables will have to be backed by hydro where available, and natural gas everywhere else. This will eventually result in a big arbitrage opportunity for anyone who can buy cheap wind or solar power and resell it in the future, i.e. electricity storage, and make money on the margin. However, very few large thermal power plants are getting built anymore in North America or Europe, whether they be nuclear or coal powered. The experience of nations like Finland with new nuclear is not comforting.

Not replacing base-load power on schedule will accelerate the take-over of solar, wind, and natural gas but probably also result in some expensive power bills as supply and demand breaks into this natural monopoly. Using natural gas for base-load isn't the wisest use for what should be our future long-distance transport fuel, IMO.

White, Organic LEDs Achieving New Efficiency Levels

2009-05-14T17:10:00.000-06:00

From the journal Nature, Reineke et al. (2009) report that they have successfully developed an organic, 'white'-light LED with superior efficiency to that of fluorescent tubes. They achieved efficiencies around 90 lumens/Watt, compared to fluroscent tubes at 70 lumens/Watt. In fact, if one is willing to accept less intense lighting, they were pushing 120 lumens/Watt.

Organic LEDs are more efficient when made in thinner layers, but this limits the total amount of light they can produce per unit area. So while you could technically paper the entire ceiling with them, as a manufacturer you wouldn't want to because the substrate costs money and so does shipping.

This report is really fascinating in terms of all the optical design elements they are incorporating to prevent wastage of electrons and photons. Or, at least, it is to me. Basically in order to get a material to emit light you have to have a bunch of energetic electrons. You have them decay/lose energy. One possible way to lose energy is in the form of a photon (i.e. light), but you could also shed energy as heat or just spread it out to other electrons (particularly if there are defects in the material). Or you could successfully emit the photon but it will just get trapped and absorbed by the LED before it gets into the air. For organic LEDs, photons being reabsorbed is the biggest problem.

The question-mark with organic LEDs remains lifetime, particularly for the blue wavelength versions. The ones discussed in this article only last a couple of hours. This was still the case when I first learned about them five years ago. Basically, they don't react well to oxygen.

Organic LEDs are not necessarily any better than conventional, semiconductor LEDs. They are being pursued because they are potentially very cheap and have the novelty of flexibility.

Night Lighting
The strategy behind efficiency in lighting is not simply in producing the most photons per Watt of applied power, but matching the emission spectrum to that of the human eye. The unit for this is the lumen, which is the perceived brightness.

Figure 1: Sensitivity of the human eye as a function of wavelength.

The objectives for day-vision, known as phototopic, and night-vision, known as scotopic, are not quite the same. Night-vision is actually more efficient, and it peaks at a wavelength of 507 nm, which is squarely in the green part of the colour spectrum. For reference, 450 nm is the centre of the blue spectrum and 630 nm would be red.

Of interest here is the use of yellow Sodium-vapour street lamps. Low-pressure sodium lamps are highly efficient in turning electricity into light, on the order of 50-80 %. However, the human eye is not very good at detecting the yellow light (589 nm) when using the rods in the eye for night-vision. As can be seen from Figure 1, night-vision is actually piss-poor at using yellow light so when driving or walking under street-lamps, you are actually using your day vision.

Table 1: Eye efficiency as a function of wavelength.

Wavelength (nm)	Photopic Efficiency (lum/W)	Scotopic Efficiency (lum/W)
470 (blue)	62	1150
507 (green)	303	1700
555 (green)	683	683
589 (yellow)	517	111

Compared to yellow sodium street lamps, a green LED could be potentially 3-times less efficient and still beat it in lumens per Watt. Of course, this isn't sufficient for driving. Depth perception requires phototopic vision, since the cones are concentrated at the centre of vision whereas night-vision is predominately peripheral. For walking paths and other applications, green LED lighting could potentially beat the pants off of sodium lamps. The ideal case would probably be a 507 nm LED with a phosphor that emits light at a longer, redder wavelength. Then both scotopic and photopic vision could be covered. Or you could just build an array that emits two wavelengths of light. In this case, the need for a blue wavelength is not quite so necessary.

Vibram Five-Fingers KSO Review

2009-05-07T09:32:00.005-06:00

So I purchased a shiny (err.. matte black) new pair of Vibram Five-finger KSOs (Keep Stuff Out) last Wednesday. I tried on the Sprint as well, which pinched my right Achilles tendon.

Note that if your feet lie in the overlap region of men's and women's shoes you can fit the shoes in 1/4" rather than 1/2" intervals, with the women's being effectively 1.5 sizes smaller than a men's. I think that fit-wise, you should gage it by pulling back on the grab-loop on the back tense. Aim for 1/2" seperation between your heel and that of the slipper.

Compared to the Sprint, the KSO has a mesh upper which is supposed to keep debris from getting in and underneath the feet. The only debris I got in mine was stuff that was already stuck to my foot when I put them on. The suspension of the KSO is sort of a pulley system that attaches at the heel, comes forward and turn to pass over the top of the foot, where it attaches with velcro. The KSO (and Flow) appears to be built on a slightly wider rand than the Sprint or Classics.

The soles are remarkably sticky. There is a waffle pattern cut into the ball and heel that probably increases the friction, particularly on pavement or other flat surfaces. Running in them is not quite the same as barefoot but the degree of protection is very good. You feel everything you're running on, and sometimes things hurt a bit but only for a second and there's no lasting pain. Like barefoot, you have to watch where you place your feet, but you have considerably more insurance whenever you make a mistake, so you can run briskly. Running on a gravel track wasn't possible for me, but trails and grass were both very enjoyable experiences. I think the most dangerous thing to avoid running on would be thorns, which could conceivably slip through the toe pads and into the side of your toes.

These things appear to be very popular, and I can immediately see why. I bought my slippers on Wednesday, the saleswoman said that they got their shipment in on Monday and had already sold 1/3rd of their stock. They are sort of on the level of things like Gore-tex, Marmot's DriClime base layers, or kernmantle rope in terms of game-changing the technology and utility of outdoor gear.

Initially there was some shelf in the big-toe of my right slipper that was irritating the nail. However, with time to work in the slipper (and some work with a nail clipper) I don't notice this anymore. Pro-tip: cut your toe nails before you go to fit these. I've found the best way to set the toes is to sit with your feet flat on the floor and then raise your heels while planting your toes.

The shoes are a little sweaty, although I think this may be a feature rather than a bug: when wet the Five-fingers suction onto your foot better.

With regards to the other models, the Classic, at least to my eyes, looked to be the ultimate camp shoe for backpacking and mountaineering. Want to get your feet out of those plastic boats? Do a technical scramble? Ford a stream? The Classic model is only slightly lighter than the Sprint or KSO, however. All Five-finger models are considerably lighter than my Chaco sandles, for example, and very compact. I also think the Flow model would make a good watershoe for kayaking.

Reading Assignment

2009-05-05T11:16:00.003-06:00

I've been digging around, looking for something to interesting to write about on an energy topic without a lot of luck. Unfortunately I think alternative energy development will slow faster than the rest of the economy. If anyone has any suggestions, please voice them.

In lieu of that, I offer some reading material:

Monsters, Inc.

An article in the New Yorker about how overgrown the finance industry as become, and why it should shrink to better fit the size of the rest of the economy. It's nice to see this meme appear in more 'respectable' corners of the world.

You Walk Wrong

An article from NY Mag on how shoes screw up the natural human walking mechanics.

Civilization's Cost: The Decline and Fall of Human Health
(requires subscription)

An short update on the status of research into the health status of paleolithic humans. Not only have humans shrunk physically since the introduction of grains to the diet some 10,000 years ago, Americans are now also shorter than in the 1950s. What the article doesn't mention is that brain volume is now much smaller than it was in the paleolithic-era too. The cynic in me wonders if brain volume has also shrunk since the 1950s.

Diet and health. What can you believe: or does bacon kill you?

Are nitrates/nitrites in meat hazardous (as opposed to nitrates/nitrites in vegetables)? David Colquhoun takes a look at the science and finds it wanting. In particular, check out the dose response curves. Any actual correlation is probably due to healthy patient bias. People who are concerned about their health don't eat bacon because they think its unhealthy, not because it necessarily is. Personally, I think that the quality of processed meats varies wildly from vendor to vendor. I buy bacon from Hutterites; it doesn't have an ingredient label.

Comparative Anatomy and Physiology Brought Up to Date

The site Beyond Vegetarianism seems to exist primarily to beat up on all fruit diets. Now there's a hard target! Nonetheless, they have some excellent articles on the likely dietary habits of paleolithic man. The article I linked goes through an extended discussion of what humans probably evolved to eat, given what we know about the anatomy of modern humans and our ancestors.

Barefoot

2009-05-03T22:38:00.000-06:00

I went sprinting barefoot for the first time ever today. I'm sure I've run fast as a kid on the beach, but I've never done so on a field, to my recollection. It was an impressively... natural movement. There was no pain at all in my feet, although afterward I noticed I abraded some of my calluses a bit. I did step on a clear plastic bottle cap at one point (that went into the garbage) but it didn't really hurt since I just skipped with the opposite foot.

I think I was just as fast as with shoes and I had far better control at top-speed. Normally when I reach top-speed I am wind-milling my feet as fast as possible and I feel distinctly like I am not in control until I stop running and free-wheel down to a stop. I tried to articulate my feet; I'm not sure how successful I was but like I said earlier, the movement was very natural. In retrospect, it seems obvious that bare foot running should feel extremely comfortable, as long as you don't puncture your foot. Of course, one of the advantages of sprints is you can easily scout your route for anything you really don't want to step on.

I've had flat feet for a long time, and used orthopedics in my shoes to correct my gait to avoid shin splints and other muscle and knee problems from running and walking. I'm very tempted to try and toughen up my feet enough that I can try some moderate distance running, say a couple of kilometers, barefoot and see if I develop shin splints.

I've been looking around for Vibram Five Fingers awhile now but no one local in Edmonton seems to carry them. One of my friends said she had spotted them at Mountain Equipment Co-op, but alas, they were not there today when I checked. They are present on the website, but they don't seem like the type of shoes one orders via mail order without fitting. C'est la vie.

Synthesis of Fat in the Liver

2009-04-17T13:38:00.003-06:00

One of my hobby horses is the idea that you have to go through the glycogen stores in your liver before your body switches into fat burning mode and that this is one of the reasons cardio-style exercise is so ineffective for fat loss on a conventional low-fat diet. The opposite state, where the liver is completely full of glycogen, is also an interesting case. In this situation the liver starts manufacturing fatty acids from glucose. This is called de novo lipogenesis in the biology vocabulary. If you break this down from Latin to English, it is "generation of new fat."

There are three main stores of fat in the body: subcutaneous (under the skin), interstitial (in-between muscle fibres), and visceral (in and around the vital organs in the belly). Of the three types, visceral fat is dangerous to health while the others are relatively benign (Porter et al., 2009).

Visceral fat, typically measured by waist-to-hip circumference ratio, or more advanced imaging techniques, is a much better predictor of future diabetes or heart disease risk than the body mass index (Westphal, 2008). For example, diabetics who are relatively thin (i.e. have a low BMI) very often have what's called central obesity (Ruderman et al., 1998) or more colloquially, are "skinny fat." Fat tissue, as it happens is efficient at producing a wide variety of hormones such as adiponectin, leptin (e.g. Angulo et al., 2004), and resistin. For want of a better explanation, packing a lot of hormone-producing fat around the vital organs is bad juju.

I pose a couple of questions for the reader to ponder:

Why is visceral (belly) fat so contrary to good health? and,

What is it in our modern diet that is driving such an excess of visceral fat?

A distinct condition whereby fat deposits around the liver cause it to dysfunction is non-alcoholic fatty liver disease (see the New England Journal of Medicine review by Angulo (2002). As the name suggests, it is characterized by the appearance of fatty deposits in the liver tissue itself. Think fois gras. In addition to the formation of fat deposits, some of the more advanced forms of chronic liver disease feature the formation of fibrosis, which is the formation of scar tissue in the liver in response to repeated, chronic injury.

Adapted from Figure 1 in (Bataller and Brenner, 2005).

Funnily enough, this condition is tightly correlated with metabolic syndrome which is in turn associated with diabetes and many other debilitating conditions. Loria et al., 2005 (free) state that:

Given that metabolic syndrome and non-alcoholic fatty liver disease affect the same insulin-resistant patients, not unexpectedly, there are amazing similarities between metabolic syndrome and non-alcoholic fatty liver disease in terms of prevalence, pathogenesis, clinical features and outcome.

Loria does state that fatty liver disease does not cause metabolic syndrome, or vice versa. Since metabolic syndrome is a catch-all description of many symptoms, I think it would be fair to describe fatty liver disease as one potential component of metabolic syndrome.

The problem with fatty liver disease really appears to be the combination of insulin resistance (from ingesting too much glucose) and high circulating triglyceride levels. From the review by Petta et al., 2009, "In fact IR [RM: insulin resistance] is the key factor in the promotion of liver fat accumulation not only by inducing an increase of liver FFA [RM: free-fatty acid] influx, but also, via hyperinsulinemia, by stimulating the activity of enzymes implicated in de novo hepatic lipogenesis."

Incidentally non-alcoholic fatty liver disease was almost certainly what Morgan Spurlock was doing to himself with his soda-laden diet in the movie Super Size Me. I noticed when watching that movie that some of his doctors (2 of 3, IIRC) didn't know that the condition existed. Non-alcoholic fatty liver disease reached incidence levels of 20-25 % in an Italian population study (Bedogni et al., 2005).

Ok, so abdominal/visceral fat causes some combination of metabolic syndrome and/or fatty liver disease. So what causes people to preferentially deposit fat around their mid-section rather than elsewhere? In researching non-alcoholic fatty liver disease, I came across the following paragraph by Postic and Girard (2008, free access), which I think is instructive:

Insulin is essential for the maintenance of carbohydrate and lipid homeostasis. Insulin is secreted by pancreatic β cells in response to increased circulating levels of glucose after a meal. A large fraction of glucose absorbed from the small intestine is immediately taken up by hepatocytes [RM: liver cells], which convert it into glycogen. However, when the liver is saturated with glycogen (roughly 5% of liver mass), any additional glucose taken up by hepatocytes is shunted into pathways leading to synthesis of fatty acids, which will be esterified into TG [RM: triglycerides] to be exported to adipose tissue as very low-density lipoproteins (VLDLs). Insulin inhibits lipolysis [RM: fat burning] in adipose tissue by inhibiting hormone-sensitive lipase (HSL), the enzyme regulating FFA [free-fatty acid] release from adipose tissue (10). Therefore, from a whole-body perspective, insulin has a “fat-sparing” effect by driving most cells to preferentially oxidize carbohydrates instead of fatty acids for energy. Insulin also regulates glucose homeostasis at many sites, reducing hepatic glucose production (HGP) (via decreased glucose biosynthesis [gluconeogenesis] and glycogen breakdown [glycogenolysis]) and increasing the rate of glucose uptake, primarily into skeletal muscle and adipose tissue.

A very interesting review that hypothesized on a link between diabetes and fructose said the following (Johnson et al., 2009):

For example, very high doses of fructose (250 g/d x 7 d) cause insulin resistance in 1 wk (147), whereas slightly lower doses (216 g/d for 4 wk) only induce insulin resistance at sites where fructokinase is highly expressed (liver and adipocyte) (148), and even lower doses (100 g/d x 4 wk) result in no insulin resistance at all (149).

If you read through any significant amount of human biology on diet it's impossible to avoid the fact that the hormone system (and insulin and growth hormone in particular) is paramount in determining whether the body is in a state of fat gain or fat loss. It's only at the nutritional level that the facts become obscured by experimenting with too many variables at once.

If you will permit me an aside, most all of our actual information about diet and nutrition comes not from the 'top-down' approach of observation or intervention trials but from the 'bottom-up' approach of trying to establish the mechanics of human physiology. I like to call the 'bottom-up' approach the 'physicsification' of biology. Most properly the 'bottom-up' approach in biology can be described as the combination of biophysics, biochemistry, and genetics (bio-computer science).

In physics, one establishes base laws that govern a system, known as first principles, and then one gradually expands on the complexity until theory adequately matches experiment. Technically any other science can be described in terms of physics, but often we are stymied by excessive computational requirements or too many unknown, confounding factors. However, gradually scientists are slowly unraveling the secrets of biology.

The main advantage of having first principles is that it allows you to construct hypotheses that are likely true, and then test them. There are a lot of famous and successful predictions in physics. Observational nutritional science, not so much. For example, Einstein's general relativity predicted that light would bend (or 'lens') around strong gravitational objects like black holes; it does.

Now, back to the topic as to what drives visceral fat accumulation...

One potential source for abdominal fat is fats produced in the liver itself, most commonly by the conversion of carbohydrates to fat. Typically the total contribution of liver-synthesized triglycerides (de novo lipogenesis) to the total number of triglycerides in the blood stream (i.e. VLDL) is relatively small, on the order of 10 % (Marques-Lopes et al., 2001). This is too small a proportion to seriously be considered as a cause of obesity.

However, if you recall from the paragraph I quoted above, the liver only really starts to kick out a lot of lipids when you exceed its capacity for storing glycogen. A study by McDevitt et al. (2001, free access) specifically looked into the case of overfeeding versus not and what effect it had on fat synthesis in the liver. They found that with overfeeding by 50 % over basal metabolic rates, de novo lipogenesis increased 2-3 fold. Overfeeding on sugar (glucose-fructose) was uniformly worse than overfeeding on glucose, but only slightly.

A study of rats fed a diet of 60 % fructose versus conventional rat chow (Ackerman et al., 2005). After five weeks, the fructose-fed rats had 15 % higher blood pressure, 198 % higher blood triglycerides, and 90 % higher blood cholesterol levels. A similar study in overweight women found similar results: when fed 25 % of calories in the form of fructose for ten weeks resulted in a 140 % increase in circulating triglyceride levels (Stanhope and Havel, 2008). These rates of sugar consumption are consistent with soda pop intake for a significant hunk of the American populace.

One question is, why does fructose (and alcohol) intake result in visceral fat, and not the more benign sub-cutaneous or intra-muscular fat? I have one possible explanation that I like to term the 'circulatory fat deposition model.' When you ingest a toxin like fructose or alcohol, the body automatically increases circulation to the vital organs (and in particular the liver) so that it can be filtered out of the blood stream. Since any ingested substance will naturally diffuse to even concentration throughout the blood, this is the only way to preferentially increase the flux of toxin to the liver.

Fructose is well known to contribute greatly to post-meal triglyceride levels (Chong et al., 2007). The liver takes fructose and produces palmatic acid (i.e. a stable saturated fat) from it. It then releases that fat into the blood stream. Since the filtering of fructose isn't instant, the circulation in the body core is still heightened. As a result, the visceral fat tissues see a higher rate of triglyceride flux than the more benign skin or muscle fat (Note: flux in a scientific sense typically means mass or volume per second — put those Star Trek thoughts out of your mind). The visceral fat, which sees the most fabricated triglycerides floating on by, also happens to absorb the most. Hence fructose tends to promote visceral fat. On the other hand, if you ingest excess calories in the form of fat, it's not any more likely to deposit around the liver than it is your thighs, so it's not nearly so dangerous.

One sees a similar effect with amateur body-builders who ingest calorie-heavy shakes and energy drinks after or during exercise where their muscles are generating a lot of lactic acid. The body increases blood flow to those muscles to remove the lactic acid, but the fat deposits inside the muscle also see a much higher flux of fat and fat-building substrate as a result. This results in a characteristic thick and pasty muscle texture without a lot of functional power. Think of well-marbled beef steak.

If this hypothesis is true then combining dietary fat with any chemical that requires extensive liver processing (e.g. caffeine, artificial sweeteners) would also tend to result in visceral fat deposition. Oh look, a prediction. I did say something about those.

This information on de novo lipogenesis, and what we know of the fat-sparing properties of insulin, provides some support to the notion that carbohydrates and fats should not be mixed in meals. It's only when you eat an excess of glucose, or any fructose, that one can transform a pure carbohydrate meal into body fat. On the other hand, if you eat fats and carbohydrates in combination, the insulin response will prevent your body from burning the fat directly. Note that if you have a dysfunctional carbohydrate metabolism (i.e. metabolic syndrome) this precept probably does not apply. Of course this advice is only useful if you are capable of restricting your caloric intake on a pure carbohydrate diet.

Fats are satiating whereas carbohydrates most definitely are not. The hormonal reason for this is related to the fact that they each use a different mechanism for regulation. With insulin, as it ramps down, it promotes the production of ghrelin, one of the primary 'appetite' hormones. Fat metabolism doesn't appear to have a similar analogue, and as a result hunger on a high-fat diet lacks the ravenous component of the insulin roller coaster.

When you think about, there's plenty of reason to believe that carbohydrates promote over-eating. By in large, most of the plant carbohydrate sources our paleolithic ancestors would have access to all mature around the same time, late summer and fall. This is a time period when it is particularly advantageous for primitive man to pack on some fat to sustain him over the winter. On the other hand, for Joe 6-Pack with his year-round supermarket access, this doesn't work out so well.

The conclusions we can draw from this body of research are that one can safely ingest glucose regularly with the aim of not saturating the liver's glycogen storage capacity. The maximum reasonable glucose intake level will vary significantly from person to person depending on general activity level and overall health based on how insulin resistant they are. Where one gets into trouble is when you overfill your liver by eating too many calories, with a significant fraction of glucose calories, or significant fructose intake (likely in the form of sugar or corn syrup). This is likely to lead insulin resistance and liver dysfunction.

Using a Neti Pot on April 1st

2009-04-01T09:32:00.004-06:00

Let's say you've just finished a world-record set of sprint intervals after taking bozolol. Now you live in a city like I do and there's a lot of 'refinery dirt' in your sinuses. How to expel it? With a Neti pot:

Direct link:www.youtube.com/watch?v=aQm7YpxgOnA

The Failure of the American Elite

2009-03-29T22:00:00.000-06:00

I would like to direct my readers to an article written by William Deresiewicz in the summer of 2008, "The Disadvantages of an Elite Education." To wet your appetite, I would like to present the conclusion:

The world that produced John Kerry and George Bush is indeed giving us our next generation of leaders. The kid who’s loading up on AP courses junior year or editing three campus publications while double-majoring, the kid whom everyone wants at their college or law school but no one wants in their classroom, the kid who doesn’t have a minute to breathe, let alone think, will soon be running a corporation or an institution or a government. She will have many achievements but little experience, great success but no vision. The disadvantage of an elite education is that it’s given us the elite we have, and the elite we’re going to have.

Deresiewicz does an excellent job of explaining why the Anglo-American elite has failed their countries so badly: they have pursued the establishment of a new class system, eradicating the existence of a meritocracy. It used to be, when you screwed up and lost trillions of dollars and indirectly put millions of people out of work, you resigned in disgrace. Not anymore, now you write whiny letters to the New York Times and rationalize away any of your responsibility. And all your peers insulate you from the negative consequences of your treacle-like mind, because they also have achieved their power and wealth with no evidence of wit or effort. It is a sad situation, because random-guy-on-the-internet-with-a-blog is clearly so much smarter. Admittedly, that is damning with faint praise; chimpanzees would also be an improvement.

I recall someone once said, with regards to NASA, "when failure is not an option, success becomes very expensive."

Feast and Fast: the dichotomy of insulin and growth hormone

2009-03-26T14:17:00.001-06:00

At its heart the human body is a machine. A very complicated machine to be sure, unknowable in completion given our current basis of knowledge, but it still obeys certain engineering concepts in the end. One of those concepts is that the operation of a machine is governed by its control system. When it comes to health, the hormonal system is the control system that governs just how well we feel. We stimulate it in various ways and it causes our bodies to react to those stimulus. Trying to pick apart these relationships is, in my opinion, the key to understanding how to obtain good health throughout our lives.

Today I'm going to write predominately about growth hormone and how it metabolizes fat. I got the idea primarily from the writings of Brad Pilon. I have not read his book; I worked from review articles in scientific journals.

Introduction

The human body has two signaling systems:

The nervous system, which primarily controls fast actions such as motion and thought.
The endocrine (or hormonal) system, which primarily handles slower processes..

The characteristic time scale of the nervous system is milliseconds. It operates on the principle of action potentials: electrical impulses driven by the fast pumping of sodium and potassium ions. Hormones do not travel down specialized pathways, instead they use the circulatory system. In the endocrine system, the characteristic time is on the order of minutes or hours as hormones decay within the blood stream. From an evolutionary perspective, the endocrine system is much older, since even bacteria use a variety of signaling peptides to control their operation. The nervous system had to await the development of such advanced animals as the mighty squid.

When it comes to metabolism, the endocrine system is the one in control. There is a portion of the nervous system that controls the gut, the autonomic nervous system, but it acts largely independently of the brain. It controls aspects like opening sphincters, e.g. stomach emptying.

If the nervous system is a digital system, then the endocrine system is very much like an analogue circuit composed of resistors, capacitors, and inductors (in biological analogue circuits these are usually called push-pots). These elements can be formed into circuits that perform various functions (amplification, integration, differentiation, etc.). However, there are many, many elements that compose the endocrine system of the human body. If you were to draw a circuit diagram of the human body it would resemble not so much a Pentium CPU as a Gordian knot with its mass of interconnections.

Conceptually the hormone system is divided into the whole-body hormones (endocrine), local tissue hormones (paracrine), and single cell hormones (autocrine). I am mostly concerned with endocrine system since it is the one that affects multiple types of tissues such as fat, muscle, and vital organs. There are certain hormones related to digestion and metabolism that can be considered the premiere, most vital hormones to control such tasks.

Examples of top-tier hormones involved in the process of eating include:

Macronutrient metabolism hormones (insulin, growth hormone)
Sex hormones (testosterone, estrogen)
Appetite hormones (ghrelin, leptin)
Basal metabolism (thyroid)
Stress hormones (cortisol, epinephrine) (Jensen et al., 1987)

Many of these hormones interrelate with each other, either directly or through the mechanism of secondary, lower-tier hormones, in a very complicated system that is difficult to pick apart. Typically the hormonal system operates on the principle of negative feedback, so if production of one hormone surges, that will in turn generate feedback that will eventually damp it back to normal levels.

For people who are trying to lose fat, a reasonable objective is to tweak one or more hormonal levels to upset the existing equilibrium. A kilo here, a kilo there, and pretty soon you're talking about real weight loss. However, like any complex system, you have to feed it the proper inputs for it to function properly: Garbage in = garbage out.

The feast and fast cycle

Insulin is the primary regulator of carbohydrate and protein metabolism. (Human) growth hormone (abbreviated GH) is the primary regulator of fatty acid metabolism. Today, we're going to talk mostly about GH since most people already know a fair amount about insulin. If you don't, you can get started with my review of Gary Taubes' book, "Good Calories, Bad Calories."

So, to review, insulin is the hormone responsible for regulating the metabolism of glucose and most amino acids (exceptions are lysine and leucine) derived from the protein in your diet that are converted to glucose for the purpose of fuel (Gröschl et al., 2003). High levels of insulin also prevent your muscles from absorbing fatty acids in the blood: the body prefers to burn the low-energy density carbohydrates first and hold onto the superior fatty acids for lean times. A person with high levels of insulin in their blood is said to be in the feasted state.

The opposite to the feasted state is the fasted state. The hormone that characterizes the fasted state is growth hormone (review: Møller and Jørgensen, 2009). The general course of progressing from feasted to fasted goes something like this:

You eat a meal with carbohydrates and protein. Digestion occurs over the course of several hours and insulin levels rise in response to the absorption of these macronutrients.
Insulin sensitive tissues absorb glucose from the blood-stream. Glucagon, a second-tier hormone, causes the liver to break down the glycogen it stores into glucose, releasing it into the blood. This slows the rate at which insulin drops.
Insulin continues to drop as the liver's supply of carbohydrate is reduced. Ghrelin (which I'll discuss later) is produced, which promotes appetite and the production of growth hormone. If the increase in appetite caused by ghrelin causes you to eat, you go back to stage 1. Otherwise, you make the transition into the fasted state as GH levels rise and blood sugar levels drop (Roth et al., 1963).

Growth hormone is basically the hormone that controls when your adipose (fat) tissues release fatty acids to be metabolized by the rest of your body. No growth hormone, no significant fat loss.

Figure 2. from Møller and Jørgensen (2009) on the interrelation of growth hormone, insulin growth factor, and insulin in the fed and fasted cycle.

However, this is not all growth hormone does. As the name suggests, GH, in conjunction with insulin-like growth factor, is involved in the growth of lean body mass: it increases the amount of protein in your muscles and vital organs, it increase the uptake of calcium by bones, etc. Growth hormone alone is insufficient to boost protein synthesis, however. I'll probably save the discussion of IGF-1 for another time (for further reading, start with Gibney, Healy, and Sönksen, 2007). In this context, growth hormone may be poorly named.

In addition to promoting fatty acid metabolism, GH shuts down the uptake of glucose into muscle tissue and stops the conversion of amino acids into glucose (Rabinowitz, Klassen, and Zieler, 1965). The fact that GH shuts down not just carbohydrate metabolism but also protein metabolism is critically important. It means that when one enters the fasted state, your muscle and organs are protected against being consumed to fuel your body (Nørrelund et al., 2006). This clearly illustrates the greatest failing of the high-carbohydrate, calorie-restricted "semi-starvation" diet that Taubes pans: if you maintain high insulin levels but insufficient calories, there's little to protect the protein in your muscles and vital organs from being consumed while your fat tissue goes untouched.

Furthermore, once a person becomes insulin resistant (and most obese individuals are), they become locked in a vicious cycle: insulin levels remain high for a long time after a meal, and stay high until the next meal, so the body never makes the transition from feasted to fasted and hence never burns any body fat. Let me reiterate: once you are obese, you will have a harder time losing body fat than a thinner individual. Unsurprisingly, growth hormone levels in obese people are depressed (Scacchi et al., 1999). The number one priority for losing weight then is improving insulin sensitivity. As an aside, this is a good reason to avoid supplementation with synthetic growth hormone: it may leave you with unnaturally elevated blood sugar for an extended period of time. Essentially growth hormone makes your tissues insulin resistant, but it normally only does so when blood glucose levels are depleted.

Body composition — whether you are lean or fat, i.e. the ratio of fat mass to lean body mass — is basically a function of the ratio of time you spend in the feasted state versus time you spend in the fasted state. Now, on the face of it, this statement is self-evident and rather useless. However, it's also very fundamental. In the natural situation, insulin and human growth hormone levels are reciprocal: GH is low when insulin is high, insulin is low when GH is high. A meta-analysis of GH found that high levels of growth hormone led to an increased basal metabolic rate of 141 [69-213] kcal/day (Liu et al., 2007). This corresponds to roughly a pound of fat per month.

What controls growth hormone levels?

So if growth hormone controls the release of fat from your fat tissues, what controls the release of growth hormone? Growth hormone is typically released in pulses from the pituitary gland. This pulsitile nature of growth hormone is similar to that of insulin in a healthy individual.

Figure 4 from Ho et al., 1988, showing the Fourier transform of GH secretion. Filled boxes are (24-hr) fasted subjects, open boxes are fed controls. Normally the horizontal axis of a Fourier transform is frequency but in this case it is period. This plot shows peaks at 110 min, 206 min, and 24 hr. The 24 hour cycle is likely caused by sleeping, the sources of the other peaks are less clear.

Growth hormone is primarily up-regulated by growth hormone releasing hormone (GHRH) and growth hormone releasing peptide, better known as ghreline. Growth hormone is primarily down-regulated by human growth inhibiting hormone (GHIH), typically known as somatostatin, and high blood glucose levels. I eagerly await the discovery of growth hormone releasing hormone releasing hormone (GHRHRH). Ok, I jest, low-levels of growth hormone and insulin stimulate GHRH.

Notice something interesting: ghrelin is an appetite controlling hormone. When you fast, GH production goes up and up and ghrelin goes down. When fasting, the hardest part is about six hours after your last meal when your insulin levels have dropped down and you have a strong appetite. However, if you get over this 'hump' you will find that your appetite largely goes away as the ghrelin circulating in your blood starts the secretion of GH. You will still get thirsty, but not ravenously hungry. I would generally recommend sleeping through this stage.

So what's the difference between controlling your body's overall insulin/GH levels very controlling your appetite to avoid binge eating? Can we actually separate the appetite hormones, leptin and ghrelin from the metabolism control hormones, insulin and growth hormone? As far as I can tell, appetite and blood sugar levels are basically the same thing. Trying to separate the two as wholly independent variables and then claiming that fat people simply lack self control when it comes to food is very very wrong. The science clearly shows that the two are deeply inter-related.

Figure 4. from Hartmann et al., 1992, showing the negative correlation between GH release and body-mass index in fasted subjects.

Production of growth hormone typically declines as we age. However, research has shown that growth hormone levels are more tightly correlated with visceral fat (belly fat) than age (Vahl et al, 1997). So do we get fat because we get old or do we get old because we get fat? Both answers appear to be correct, each to a degree. No one will live forever, but most of us would like to age gracefully. I'm about a decade younger than I was at this time one year ago.

Real-world means of increasing growth hormone levels

There are three basic ways to increase the amount of GH your body produces:

Get adequate sleep. GH production spikes during sleep. Try not to eat before bedtime.
Fast occasionally, for relatively short durations.
Conduct intense exercise. Don't eat before or during your exercise.

'Intense' exercise in this context means you should exceed 75 % of your ~~VO2 max~~ lactate threshold (Pritzlaff et al., 1999). ~~VO2 max~~ Lactate threshold is the level at which the demands of your exercise exceeds your body's ability to breath in oxygen, causing the body to go anaerobic and produce lactic acid. Note that ~~VO2 max~~ lactate threshold is for your whole body, so you need to exercise your whole body or at least the biggest muscles (core, glutes, quads). You can do bicep curls until your arms fall off but since they're small muscles you won't get much of a GH boost from doing so. The best exercise for putting your whole body into the anaerobic threshold is probably sprint intervals.

Figure 1. from Pritzlaff et al., showing GH secretion pulses as a function of lactate threshold (LT) reached.

Of course, (2) and (3) can be combined. A word of warning, if you exercise hard at the end of a fast, be prepared for sore muscles (i.e. delayed onset muscle soreness) the next day.

A low-carbohydrate diet may have the advantage in this situation as the overall insulin pulse should be small and of shorter duration. The reason is fairly obvious: the body's tissues will be less insulin resistant and hence absorb glucose from the blood stream more readily. Hence one should enter the fasted state quicker after a low-carbohydrate diet than not. The more time you spend in the fasted state, the faster you're going to shed body fat.

The $64,000 dollar question is then, what effect does dietary fat have on growth hormone secretion? It appears that dietary fat intake increases the production of somatostatin from the gut, otherwise known as growth-hormone inhibiting hormone, although somatostatin down-regulates many many other hormones (Cappon et al., 1993). Anecdotal evidence from people who regularly fast is that fasting is easier to handle on a low-carbohydrate diet than a low-fat diet. I dug around for awhile on PubMed, but I wasn't able to find any research where subjects were fed diets of pure glucose and pure triglycerides and then their transition from feasted to fasted tested. It would be a good Master's thesis for someone if it really hasn't been done before. I did find tests that tested intravenously applied fatty acids in fasting but since somatostatin is produced by the digestive system their relevance isn't clear. The Hartman study from 1992 seems to be the best starting point for this line of research.

References
in alphabetical order:

Cappon JP, et al. "Acute effects of high fat and high glucose meals on the growth hormone response to exercise." J Clin Endocrinol Metab. 1993 Jun;76(6):1418-22.

Gibney J, Healy ML, Sönksen PH. "The growth hormone/insulin-like growth factor-I axis in exercise and sport." Endocr Rev. 2007 Oct;28(6):603-24.

Gröschl M, et al., "Endocrine responses to the oral ingestion of a physiological dose of essential amino acids in humans.", J Endocrinol. 2003 Nov;179(2):237-44.

Hartman ML, et al., "Augmented growth hormone (GH) secretory burst frequency and amplitude mediate enhanced GH secretion during a two-day fast in normal men." J Clin Endocrinol Metab. 1992 Apr;74(4):757-65.

Ho KY, et al. "Fasting enhances growth hormone secretion and amplifies the complex rhythms of growth hormone secretion in man."J Clin Invest. 1988 Apr;81(4):968-75.

Jensen MD, et al., "Lipolysis during fasting. Decreased suppression by insulin and increased stimulation by epinephrine." J Clin Invest. 1987 Jan;79(1):207-13.

Liu H, et al. "Systematic review: the effects of growth hormone on athletic performance."
Ann Intern Med. 2008 May 20;148(10):747-58.

Pritzlaff CJ, et al. "Impact of acute exercise intensity on pulsatile growth hormone release in men." J Appl Physiol. 1999 Aug;87(2):498-504.

Møller N, Jørgensen JO, "Effects of Growth Hormone on Glucose, Lipid, and Protein Metabolism in Human Subjects." Endocr Rev. 2009 Mar 19.

Nørrelund H, et al., "The protein-retaining effects of growth hormone during fasting involve inhibition of muscle-protein breakdown." Diabetes. 2001 Jan;50(1):96-104.

Jesse Roth, et al., "Hypoglycemia: A Potent Stimulus to Secretion of Growth Hormone." Science 140(3570):987 - 988 (May 1963).

Scacchi M, Pincelli AI, Cavagnini F. "Growth hormone in obesity." Int J Obes Relat Metab Disord. 1999 Mar;23(3):260-71.

Vahl N, et al., "Abdominal adiposity rather than age and sex predicts mass and regularity of GH secretion in healthy adults." Am J Physiol. 1997 Jun;272(6 Pt 1):E1108-16.

David Rabinowitz, Gerald A. Klassen and Kenneth L. Zierler, "Effect of Human Growth Hormone on Muscle and Adipose Tissue Metabolism in the Forearm of Man." J. Clin. Invest. 44(1): 51-61 (1965).

Economic Limits to Energy Reserves

2009-03-19T12:03:00.001-06:00

If you have a passing familiarity with energy policy, you probably are aware that the scale of potentially available resources is enormous. For example, the USA is purported to maintain coal reserves sufficient for 250 years of consumption, or 1600-3600 billion metric tons. From wind, the total world resource that is considered to be commercially viable is about 72 TerraWatts. However, that figure only includes the wind resources that exceed some average velocity (probably 7 m/s) so the actual total resource is somewhere around 500 TW. An enormous figure.

The viability of renewable power is largely a function of the price of fossil fuel commodities, the action of government in regulation and subsidy/taxation, and the technology level of the renewable sector. The conception that renewable power will be composed of a mélange of many different sources does not fully illustrate the likely outcome.

The term, commercially viable, then is key. What matters is not how big a resource is in absolute terms, but how that resource is distributed in terms of quality relative to alternative energy resources.

One possible metric for energy resource quality would be the EROEI (Energy Return On Energy Invested) which is especially popular in the Peak Oil community. It is an expression which can be derived in engineering terms so it is quantitative. However, the metric that really matters is the economic one: how many dollars do I have to spend to get my unit of energy? How can I further parametrize an alternative energy resource to evaluate when it will become economical to exploit?

Inertia and vested interests will have an influence over the short-term but eventually the cheaper source of energy will win. It's much more fuzzy than EROEI, since adding money adds many more degrees of freedom (i.e. value of fiat currency, cost of credit, cost of technology, etc.) and anything money related has a big rationalization factor, but it's fundamentally closer to the truth. If the EROEI metric was the determining factor, we'd all be powered by hydroelectric dams (and yes I am aware that after you amortize, hydro power is dirt cheap... smart ass).

The real metric then for energy quality is going to be the rate of return in dollars, not energy. Unfortunately, dollars per unit of energy is going to be a datum with many degrees of freedom behind it, making analysis complicated and prone to change on a month to month basis. Still, we can construct some hand-waving arguments based on best guesstimates to make some general conclusions.

Figure 1: Schematic of renewable energy resource economic distribution. Not to scale, seriously based on established data, etc. but rather a illustration for the eye. There's no reason for these curves to be symmetrical, it just looks better.

Most resources can be described as a sharp peak with heavy tails. For wind, you have some select areas where the terrain funnels katabatic winds coming off of mountain ranges and you find a strong, consistent wind resource. On the other hand, much of the Earth is covered in forests which increase the surface drag and results in a poor quality wind resource. On the geothermal power front, you have a few select areas where vents circulate magma from the Earth's mantle near to the surface and a lot of heat power can be extracted. However, most deep geothermal is going to be pulling heat energy out of the crust which isn't replenished quickly. Most rocks only conduct around 30 mW/m² so it's easy to exhaust the resource. It's not clear, then, if deep geothermal can easily amortize the capital costs of drilling. Solar is an exception, in that not only does it dwarf all other resources in total potential but it's also very stubby.

If you look at the scale of various renewable and non-renewable power sources it quickly becomes obvious that solar dwarfs them all. There is about 190000 TW of solar power incident on the earth at any one time. Even when you factor in scattering from the atmosphere and clouds, it's still ~ 125x greater than the wind resource. Moreover, solar is also the most uniformly distributed. The best solar resources in the world, such as Arizona and North Africa, only receive about 3x more power than cloudy Northern Germany. This means that any graph of solar resource quality as a function of the total available resource is very squat and shallow. It's the Olympus Mons of power quality-potential curves. So why am I going on and on about solar? Well, it provides an economic floor to all other sources of power. Any portion of a resource that economically falls below the top of the solar curve, won't be significantly exploited, due to the extreme width of the solar curve.

The significance of the above statement is mostly of interest as a tool for formulating public energy policy. Should all alternative energy technologies be pursued with the aid of the public purse? Primary research at the academic level should not be funded on the whim of politicians, but when it comes to issues like production subsidies, the introduction of politics is unavoidable. Thus, I would like to propose a check-list for all those prospective deciders out there (and of course investors in the private funding world):

How large is the renewable resource that lies significantly above the solar resource and how does that compare to the amount of proposed investment? Note that this will change significantly from region to region. Britain isn't a great solar resource, but it has a much larger wave power resource than most. So for Britain you have a wider effective wave power peak and a lower solar base-line.
Is there a significant body of academic research (typically 10-20 years) behind the concept or is it pie in the sky? Too many big energy ideas/start-ups try and do research and development without doing the research part. Needless to say, it usually ends in tears. Lithium-ion iron-phosphate batteries didn't pop out out of the ether, and neither did First Solar.
What sort of (general) technologies developments on on the horizon that may effect the size and shape of the resource's economic curve? This is a really tough question for a politician to answer unfortunately. My advice is to keep it simple: only the really big changes matter on a macro scale.
Does the technology deliver power at night? Statistically, wind and solar power have an almost identical standard deviation, the difference is solar is predictable. Looking forward, it seems inevitable that electrical power will be cheaper during the day than at night. This may necessitate, for example, plug-ins at work — we already have such things in Edmonton, but for powering the block heater in your car so the oil pan doesn't freeze into a solid pane of grease.

And what of the non-renewable resources? Well those curves are actively being consumed, with the highest quality reserves (i.e. the peaks of the mountains) going first. Of course, with improving technology, their are fossil reserves that are becoming more economic at the same time. It took a fairly enormous investment to get the oil sands of Alberta viable, but here we are now, making oil from asphalt.

There are also a number of more auxiliary issues that can have a significant impact on how edit( economical a particular technology can be in a given locale. Some are simply a function of geography, such as how concentrating solar power only works in terrain that sees little cloud cover. ) These parameters make the situation fuzzier than before, but we can at least account for them in some qualitative, if inadequate, sense. An example that I've discussed is the increased speed of deployment and improvement of energy technologies that can be deployed in an incremental fashion.

Inertia of existing technologies is one of the most important parameters. Inertia in terms of an existing energy technology can be summed up as: embedded capital costs. As an example, buying an electric car or a plug-in hybrid costs quite a lot of money. Even buying a depreciated used SUV compared to a new Prius requires a huge number of miles driven to recoup the price premium between the two. The nature of inertia means that as the best of the fossil resources continue to be consumed, there will naturally be some overshoot before the renewables come to the fore.

Arbitrage opportunities should also be a great way of making money in the future. The giant disadvantage of renewable technologies like photovoltaic solar and wind is that they are not dispatchable (and in the case of wind, not reliably predictable). If 100 % of your generating capacity has to be backed with natural gas turbines, that adds a great deal of capital cost to your power generating infrastructure. I.e. it makes wind more expensive than the cost of the turbines alone would imply. However, balancing supply and demand with a reserve of turbines is probably the most expensive path you could take.

If you are an investor and want to start a new thin-film photovoltaic company, you are probably too late to catch the leaders. The depression of global trade and financial services will slow down the existing photovoltaic manufacturers, but you still have to navigate an uncertain minefield of failed technologies and patents. However, there's still plenty of opportunity to find niche applications to match daytime electricity generation to nighttime demand. Plug-in hybrids are generally seen as an excellent means of smoothing out the supply and demand curves, especially because they can justify a higher battery cost since they are purchased primarily for driving and not regulating the electrical grid. There are also other demand shaping potential means of arbitrage out there.

Richard Florida on Economic Resets

2009-02-24T12:03:00.003-07:00

I recently listened to an interesting talk by U of Toronto's Richard Florida on recessions and where do we go from here? Florida's idea is that recessions act as resets for the economy, allowing the big old companies to die off so that new operations can grow and take their place.
Perhaps a better analogy is 'forest fire'. The US stimulus plan is specifically failing to eliminate the failures. As the Russians would say, don't reinforce failure.

Richard Florida on the Current podcast

The podcast does come across as a bit of a pump job for the greater Toronto area. I generally agree with his thesis, however. Royal Bank logged a C$1.14 billion profit in 1Q2009, and CIBC was similar (C$141 million with a C$708 million write-down). So yes, the Canadian banks are doing very well, relatively speaking. He's totally correct that too much money has been spent on housing and consumer goods. I found it interesting primarily because Florida is suggesting ways forward. There's too much hand wringing going on these days.

Canada's biggest weaknesses in my opinion are a lack of consistent funding for the 4th sector of the economy (R&D) and lack of diversity in some areas (i.e. too much reliance on resource extraction). For example, the Canadian government is inordinately fond of funding infrastructure and equipment purchases for universities rather than providing on-going support for salaries and maintenance. Greater emphasis should be placed on processing raw materials before they exit the country. Why do we export raw logs from time to time?

Trial Lead Balloons

2009-02-22T21:12:00.002-07:00

It's been amusing over the past month or so watching the new Treasury Secretary, Tim Geither, float off a new trial balloon every weekend on a new plan to deal with the insolvency of the US financial sector. I personally, don't see any easy way out. The only reasonable solution appears to be nationalization, and I don't pretend it will be easy for those involved in managing it (last September):

Bank of America, CitiGroup, and JP Morgan Chase have all been busy building the Jenga tower higher (see making the pie higher) in the effort to become too ginormous to fail. Clearly they all expect to be bailed out, which is a pretty amoral way to run a business. "Bail us out or your retirement savings get it!" The appropriate response at this stage is to raise their moral hazard one and audit them, find out that, "Surprize, you're broke!" and nationalize the lot of them temporarily. Cashier the executives, amalgamate the trash from all three and quarantine it, then start breaking them into non-antitrust sized chunks and IPO them off in sequence.

So now, after attempting to float many balloons full of lead, we are finally getting there. Citi now wants the government to buy 40 % of its stock, stopping just short of nationalization. Does anyone really believe we'll be done at that point?

The only question I have, is were these leaks that came from the Treasury real ideas or was Geither just buying time and making an appearance of exhausting all the alternatives? Afterall, nationalization isn't part of the American culture. Cultures change; sometimes tumulteously, sometimes without even noticing.

All Medical Science is Wrong within a 95 % Confidence Intervalor: A Review of Taubes' "Good Calories, Bad Calories"

2009-02-08T10:55:00.001-07:00

Recently I read a very impressive book by Gary Taubes, previously a reporter for the journal Science. The work in question is, "Good Calories, Bad Calories."' In the book, Taubes collects research to challenge the common knowledge of nutrition: that fat is bad for you, that we should eat polyunsaturated vegetable oils, that we should exercise for sixty minutes a day, etc.

The genesis of Taubes' book is an article he wrote for the NY Times in 2003. Five years later, Good Calories, Bad Calories was published. As background, there is a video of Taubes here where he overviews his thesis (1 hour 11 minutes, not safe for work since there are pictures of naked obese individuals) and adds a few pieces that were not in the book. Even if you have read the book, I recommend listening to the lecture. You can see from the video, Taubes is very solidly built.

In return for knocking down a bunch of accepted "common knowledge" hypotheses , Taubes presents ten new hypotheses (p.454) and I will add a few more than I extracted from reading the book:

Dietary fat, whether saturated or not, is not a cause of obesity, heart disease, or any other chronic disease of civilization.
The problem is the carbohydrates in the diet, their effect on insulin secretion, and thus the hormonal regulation of homeostasis—the entire harmonic ensemble of the human body. The more easily digestible and refined the carbohydrates, the greater the effect on our health, weight, and well-being.
Sugars—sucrose and high-fructose corn syrup specifically—are particularly harmful, probably because of the combination of fructose and glucose simultaneously elevates insulin levels while overloading the liver with carbohydrates.
Through their direct effect on insulin and blood sugar, refined carbohydrates, starches, and sugars are the dietary cause of coronary heart disease and diabetes. They are the most likely dietary causes of cancer, Alzheimer's diseases, and the other chronic diseases of civilization.
Obesity is a disorder of excess fat accumulation, not overeating, and not sedentary behavior.
Consuming excess calories does not cause us to grow fatter, any more than it causes a child of grow taller. Expending more energy than we consume does not lead to long-term weight loss; it leads to hunger.
Fattening and obesity are caused by an imbalance—a disequilibrium—in the hormonal regulation of adipose tissue and fat metabolism. Fat synthesis and storage exceed the mobilization of fat from the adipose tissue and its subsequent oxidation. We become leaner when the hormonal regulation of the fat tissue reverses the balance.
Insulin is the primary regulator of fat storage. When insulin levels are elevated—either chronically of after a meal—we accumulate fat in our fat tissue. When insulin levels fall, we release fat from our fat tissue and use it for fuel.
By stimulating insulin secretion, carbohydrates make us fat and ultimately cause obesity. The fewer carbohydrates we consume, the leaner we will be.
By driving fat accumulation, carbohydrates also increase hunger and decrease the amount of energy we expend in metabolism and physical activity.

RM: Man, being the premier predator on the planet, evolved to eat a diet high in fat (and in particular the saturated and mono-unsaturated fat found in animal tissue). In the absence of clinical data, we should endeavor to structure our diet to be similar to that we evolved eating, prior to the introduction of agriculture approximately 10,000 BCE.

RM: Advanced Glycation End-products (abbreviated AGEs) may be a cause or byproduct of the oxidative stress that causes aging and many of the maladies associated with it.

RM: A low-calorie, high-carbohydrate diet will make you lethargic as chronically high insulin levels will try to convert glucose to fat while not leaving sufficient calories for the remainder of your basal metabolism. In comparison, low-carbohydrate, moderate-calorie diet will leave you energetic and lean.

One cannot help but wonder how a number of the weak hypotheses that Taubes explores came to become common knowledge in the field of nutrition? Taubes paints a picture of a few egotistical researchers who were able to effect what was essentially scientific fraud, by fitting their bias to the data rather than examining it critically. In Taubes words (p. 451), "it is difficult to use the term "scientist" to describe those individuals who work in these disciples [ed: nutrition, chronic disease, and obesity], and, indeed, I have activity avoided doing so in this book."

More importantly, once they established the common wisdom, they were able to better direct government funding to only support their hypotheses. I came to a somewhat different conclusion to Taubes, in that I see the puritanical aspects of American culture in the formation of these bogus hypotheses. For example, Taubes' quotes Jean Mayer, one of the fieriest preacher that lack of exercise causes obesity, in a 1955 The Atlantic magazine article:

Obesity, it is flatly stated, comes from eating too much and that is all there is to it. Any attempt to search for causes deeper than self-indulgence can only giver support to patients already seeking every possible means to evade their own responsibility.

Like I said, puritanical. This line of thinking can be traced all the way back to people like Sylvester Graham in the 1800s. The idea that cardiac disease might be caused by inflammation and bacterial infection and not by living a sinful life has been remarkably slow to percolate through the American consciousnesses yet it is well understood to be the case now. Obesity is probably not dissimilar.

Prior to my introduction to the world of low-carbohydrate diet, I hadn't paid too much attention to nutritional science. I worked on biophysics, where I formed the opinion that medical science was mostly garbage. This isn't largely the fault of the scientists involved; there's little opportunity for adequate learning though experience of repeated experiments and the systems involved are extraordinarily complex. As a physicist, if I get an correlation coefficient, R² < 0.9997 in an experiment, I would consider that a poor result. A nutritional researcher working with human patients cannot even dream of achieving the degree of control or characterization I can, and their data are overloaded with spurious noise.

Researchers in the soft sciences typically do not have sufficient math skills to understand the statistical methods that are they are using to evaluate their data. I've lost track of how many times I've seen evaluations of the mean and standard deviation for distributions that are clearly not normal (also known as Gaussian). Don't even get me started on p-values. More importantly, very few medical studies attempt to test a single hypothesis. Far too many studies will compare apples to bananas, rather than apples to no apples, or they'll compare apples, oranges, and bananas to no fruit. Making conclusions from such messily designed experiments is rife with the potential for misinterpretation. Drug studies are often an exception.

The Insulin Hypothesis

The central thesis of "Good Calories, Bad Calories" is that chronically elevated insulin levels is likely responsibly for the, "diseases of Civilization," such as diabetes, heart disease, cancer, etc. I put, "diseases of Civilization," in scare quotes because although these diseases are absent from primitive cultures, it is obnoxious to explain to individuals of non-Western ancestry that they do not suffer from these diseases because they are uncivilized (Burkitt and Trowell). Wikipedia calls these Lifestyle diseases, which seems a more apt terminology.

Let me be clear: nothing about Taubes' insulin hypotheses are actually owned by Taubes. The idea that carbohydrates are fattening has been known from well before the discovery insulin. The knowledge that diabetes could be cured by avoiding carbohydrates was also known before the discovery of insulin. Taubes is merely going over old research and bringing it together as a strong argument.

When viewed through the prism of evolutionary science, this makes a lot of sense. Fat stores would have been necessary to maintain the organism when hunting failed and there were insufficient edible plants. Carbohydrate stores, on the other hand, requires a huge amount of water to act as solvent. Each gram of glycogen that you store needs ~2.5 g of water solvent, so at 4 kcal/g carb, you have an effective storage capacity of 4 kcal/3.5 g = 1.15 kcal/g. Fat is 9 kcal/g and it doesn't require a solvent when stored in adipose tissue so that's a 7-fold increase in storage capacity. Fat is a vastly superior way to store energy.

So what was the source of carbohydrates for humans before we developed agriculture? Presumably wild fruit. Fruit matures, more or less, all at once as anyone who has owned an apple tree knows, and rots rather quickly after it has fallen off the tree. Thus, when fruit is available, it is perfectly logical to gorge oneself and use all that easily harvested sugar energy to synthesize fat storage for consumption in lean times. Thus the evolutionary reason for our sweet-tooth is easily explained.

Effectively, we evolved to preferentially burn-off the glycogen in our muscles and liver before we switched to fat. There's ~300 g of carbohydrates stored in the body, which corresponds to ~1500 kcal. Just you try and burn 1500 calories via a cardio-workout. Eating three square meals a day with carbs at every serving implies that you will never burn through your reserves and hence the body will never resort to burning fat.

So, briefly, how does one use these conclusions to achieve a healthy low body fat (and BTW, waist circumference is the #1 metric for heart disease)? Certainly not by the standard, low-calorie, high-carbohydrate diet (semi-starvation diet in Taubes' terms) which has been nothing but a dismal failure from a clinical and practical perspective. There are three basic strategies:

Very long and very slow exercise (4+ hrs), typically hiking or cycling in my case. This is a far cry from the type of anaerobic-limit cardio exercise one typically sees recommended, for example, by the American Heart Association. There is a yawning gulf between walking and jogging. I personally approve of anaerobic exercise, such as sprint intervals or plyometrics.
Consistently eat carbohydrates at a low enough level that the brain (which prefers glucose over ketones) consumes the entirety of carbohydrates that you eat, leaving the body to burn ketones. This is a slow process.
Periodically fast for an extended period of time so that your basal metabolism burns through your glycogen reserve and then begins to mobilize fat. This is not a calorie reduction method, rather you are simply not eating three times a day (on average), and as such having more extremely calories negative and calorie positive periods.

Eventually, everyone will plateau at a certain level of body fat. The number of fat cells in your body is more or less set by age twenty; dieting simply changes how full they are. Eventually, fat cells will revolt and through leptin demand a stronger appetite. So is there any need at all for carbohydrates in the diet?

Grains are the ultimate, "empty calories," in terms of micronutrients. Not only to grains have essentially no micronutrients (they are fortified for a reason), they also have a number of anti-nutrients that impede the uptake of nutrients from vegetables and animal tissue. From a health perspective, there's no need to eat grains or starchy vegetables such as potatoes.

Typically one might recommend 50-80 grams per day simply to supply the brain with glucose, but even this is not strictly necessary as the liver can convert fatty acids to glycogen. Of course, people who are obese are likely suffering from hyperinsulina (insulin resistance/metabolic syndrome) and as such may suffer discomfort upon undertaking an low-carbohydrate diet.

For the record, I dropped 22 lbs. (20 lbs. by August 2008) going from a BMI of 24.7 in May 2008 to 21.4 as of now. I've been as low as 143 lbs. in the past but I was never able to maintain that; typically I got to such a weight by bicycling 12+ hours a week at 30-40 km/h. I'm now sitting at 145 lbs. (edit: now 144 lbs.), in January (ed. February), in Edmonton, with no chronic cardio. This is a totally new scenario for me as I almost always put on 10 lbs. over winter.

When I put on weight it is prominently in the form of visceral and subcutaneous fat; I've never had significant interstitial muscular fat so I've always had relatively hard muscles. I try and aim for a distribution of 60 % fat, 25 % protein, and 15 % carbohydrate in my diet. Since my blood sugar/insulin isn't riding a roller coaster up and down throughout the day, I generally don't get hungry. I am much better at concentrating throughout the course of the day, irrelevant of when I last ate and I've found that my thinking process is much cleaner and crisper.

Unanswered Questions

Taubes criticizes a number of scientists in his book for over-simplifying the science of physiology in an effort to understand it. In that respect, reducing the argument of "Good Calories, Bad Calories" to carbohydrates-bad, fat-good is probably guilty of the same offense.

Taubes dose throw us a couple of bones, in the form of some of the more buzzword lines of research in nutrition today. One is Advanced Glycation End-products (AGEs); we know that AGEs are tightly correlated to age. From what I've read, thus far the early reports on AGEs are similar to those on cholesterol fifty years prior: lot's of smoke, but no fire. Efforts to link AGEs to ingestion of AGE materials (e.g. burned meat) has thus far failed, IMO.

Fat-soluble vitamins

One aspect of carbohydrate/fat balance that Taubes does not cover is the impact of the fat-soluble micro-nutrients. We, as humans, have given up our abilities to fabricate the majority of vitamins that we need in favour of having big brains. We are very poor at transforming one complex of a vitamin (typically the vegetable source) to the type we need to function.

As our consumption of fats has declined in favour of carbohydrate the quality of fats that we eat has also declined. As such, we are typically deficient in fat soluble vitamins, in particular D3 and K2. Not only we as a society getting far less vitamin D3 from sun exposure, but the animals we eat are also more often than not locked in a barn eating corn, so they also contain less fat soluble vitamin. When you consider that your skin can produce something like 10,000 IU of D3 in an hour compared to a multivitamin at 400 IU, it's not a giant stretch to believe that the majority of Western people are going through life deficient in it. K2 is similar; butter is a good source, but butter has been demonized by our corporate media.

Poly-unsaturated Fats

Palmitic acid is the fatty acid that your liver manufactures from sugars. In fact, the only fat humans evolved to burn for fuel directly is saturated fat. All other fats we trans-saturate first, and then burn. It would seem strange then given the complexity of the human body that we evolved to preferentially make saturated fats over polyunsaturates, unless we prefer saturated fat because it is more stable and hence less prone to oxidation.

The canard that saturated fats, "clog your arteries," is just that, bogus. The medical establishment has never believed this since they knew full well plaques form inside the arterial wall, not on the surface. Why this idea was allowed to percolate through the public, I do not know.

This begs the question, should we eat polyunsaturates at all? They are, after all, highly unstable and very easily oxidized. I ask a question: when was the last time you bought a nut oil, e.g. walnut or sesame, at the supermarket? Was is refrigerated on the shelf? Was is in a brown bottle to prevent light from damaging the polyunsaturated fat? I've seen flax oil sold in such a fashion but no other. Much of the fat we eat is oxidized by the time it reaches our mouths.

Fish oil (omega-3) is clearly doing people a lot of good, even if it sits in a cylinder for months. A lot of people do feel that we get far too much Linoleic acid, an Omega-6 essential pre-cursor, from soy, corn, safflower and other vegetable oils. It does, after all, have a significant hormonal effect.

This has led some to suggest that one should balance omega-3 and omega-6 consumption. I.e. if your omega-3 consumption is 3-4 one gram capsules of fish oil a day, then you shouldn't eat more than ~5-10 grams of vegetable oil. The American Heart Association apparently felt the need to push out an editorial recommending that the diet 5-10 % of calories should be in the form of omega-6 polyunsaturates to counter this meme. The fascinating thing about this editorial is that there are 81 references in 3 pages (which is beyond extreme), yet, there are no references — no studies, no research — that support the advised level of dietary intake. Take a look at the article (it's free access), it's quite amazing.

Rebuttal: Conservation of Energy

One of Taubes' chapters deals with the idea that energy balance in humans can be reduced to the First Law of Thermodynamics:

ΔE = E_in - E_out

I was somewhat confused to see this Surely the nutritional scientists did not not really believe this, right? I mean, any idiot undergraduate students knows that the 1st Law is only useful in a closed system, and humans live on the planet Earth, not in an insulated box. Right?

Enter a rebuttal by G. Bray in the journal Obesity Reviews. Bray is a to be a major obesity researcher and one of the 2nd tier villains in the book. Taubes relates a story of Bray excising a section of a British report on obesity, where Bray removed the material pertaining to the relationship between insulin and obesity. He clearly has editorial support to make his case. Bray is one of the second-tier villains in Taubes' book. Taubes has a footnote (p. 421), which suggests that Bray actively suppressed the carbohydrate-insulin hypothesis.

* According to Novin, when he wrote up his presentation for the conference proceedings Bray removed the last four pages, all of which were on the link between carbohydrates, insulin, hunger, and weight gain. "I couldn't believe he would make that kind of arbitrary decision," Novin said.

Unfortunately, to a physicist this energy balance hypothesis looks like a silly hand-waving exercise, not a serious argument. Frankly I was flabbergasted when I first read this article. This conservation of energy argument is on the same scientific level as the ridiculous "drink cold water to lose weight" idiocy. A human organism is:

Not in thermal equilibrium with their environment. Last time I checked I have a body temperature around 38 °C and spend most of my time in 21 °C rooms.
Capable of significant mass flows (e.g. respiration).
Capable of sequestering entropy (e.g. protein synthesis).

Is wearing a sweater fattening (by insulating you from your environment)? Here's a quote from the rebuttal,

Let me make my position very clear. Obesity is the result of a prolonged small positive energy surplus with fat storage as the result. An energy deficit produces weight loss and tips the balance in the opposite direction from overeating.

According Bray's thermodynamics argument, wearing sweaters makes you fat. This illustrates the greatest fallacy of trying to apply the 1st Law to a human: it makes the implication that living organisms consume kilocalories for the purpose of generating heat rather than perform useful work (i.e. breathing, contracting cardio and skeletal muscle, generating nervous action pulses, etc.). In reality heat is the waste product of basal metabolism. The first law does not distinguish between different types of energy. Heat, work are all equal under the First Law of Thermodynamics.

Applying the 1st Law to living organisms is Proof by Tautology. Yes, 1 + 1 = 2, but this tells us absolutely nothing about the underlying mechanics. The 1st Law does not (I repeat N-O-T) tell us whether you store excess energy in the form of fat, or bleed it off into the atmosphere by dilating blood vessels next to the skin, sweating, etc. To do so would require an accounting of entropy.

What would a semi-rigorous description of the thermodynamics of a human organism look like? Look at the title strip on the top of the page. See that equation in the background?

This type of equation would be a bare starting point for energy balance in a complex system like a living organism. Good luck actually accounting for all the terms. Those Σs are sums.

If anyone else has seen any other critical reviews to "Good Calories, Bad Calories," please feel free to post them in comments and I will take a look.

Environmental Aspects

As most people are aware, feedlot meat production produces copious amounts of greenhouse gases, both in terms of the fertilizer required to grow the corn to feed the animals, and the methane produced by rudiment digestion. This provides a bit of a moral quandary, in that feedlot meat is not readily described as sustainable.

First, greenhouse gases are perfectly fungible, so since my personal greenhouse gas emissions are about 1/3 normal, I am still well under any proposed quota. Although this has an aspect of the "beer refrigerator paradox" to it, it's still valid if the numbers work out.

Second, as it happens, I do live in Alberta and I can and do buy pasture-raised meat. Meat that feeds on unfertilized prairie grasses not only has a different composition but a far lower greenhouse potential. The visual difference between feedlot beef and pasture Elk is fairly startling. About 50 - 65 % of what I buy is via individual farmers at the market. In particular, I try to ensure that all the offal (organ meats) that I buy are from pastured, hormone and antibiotic-free animals since they are more likely to concentrate in the organs.

It's true that if everyone tried to by pasture-fed meat, there would not be enough to go around, but at the moment it is sustainable for me.

Misplaced Priorities

2009-01-22T11:52:00.002-07:00

So the Securities Exchange Commission is said to be probing Apple over accusations that they may have misled the public over the state of Steve Jobs' health.

Let's play a word association game:

Pancreatic cancer
+
Corporate executive
=
?Healthy?

One can imagine that if Jobs had cancer in the Islets of Langerhans, the portion of the pancreas responsible for insulin regulation, that yes, he might have some diabetic-like health issues associated with that. Doesn't the SEC have something better to do? E.g. meanwhile we learn that Merrill-Lynch maneuvered to deliver $3 billion inbonuses before being bought-out by Bank of America. Merrill-Lynch lost over $20 billion in that quarter, and BoA is demanding that it be bailed out by the US taxpayer now for the same amount. This idea that financial companies need to pay out bonuses to retain "top talent" during a period when the financial sector is undergoing a severe contraction is a canard. Where are they going to go work, the construction industry?

Bitumen-producer Suncor Posts Significant Loss

2009-01-20T16:34:00.005-07:00

Via Nathan Vanderklippe at the Globe and Mail, we learn that Suncor, one of the original and bigger oil sands producers, has posted a C$215 million loss for the 4th quarter of 2008.

The price of oil has fallen since then. I don't imagine the other producers will be doing much better, although Suncor does burn the least amount of natural gas and predominately runs an open-pit mine to the best of my knowledge. As I've pointed out previously, the marginal cost-of-production for synthetic crude from bitumen is around $50/bbl. The article is claiming it's more like $36/bbl although that may not include refining. If the oil sands of Alberta shut down due to extended low prices, that's approximately $1.3 million barrels per day taken off the market.

Column-like Films of Silicon for Battery Applications

2009-01-07T13:01:00.008-07:00

About a year-ago I relayed the story of Chan's work on using silicon nanowires as a potential anode material for Lithium-ion batteries. Silicon can store some ten-times more charge than Carbon, the current industry standard, but this comes at the expense of a huge volume change. The difference in volume between charged and uncharged is 300 % for Si. Just to give you an idea, the alloy of Lithium and Silicon that's formed is Li₁₄Si₄ from metallic Si. The article from Nature Nano suggested that forming the silicon into high aspect-ratio wires would allow the silicon freedom to expand along the long-axis of the wire and hence be less likely to physically break and no longer have a physical, conductive pathway to the anode.

In general, the lifetime of a battery is determined by how great of a volume change it undergoes when cycling from the charged to uncharged state and vice versa. Volume changes imply stress and the gradual introduction of defects that can trap electrons and reduce electrical conductivity. For LiFePO₄ cathodes, the volume change is around 4-7 %, but this is a crystalline material. Silicon nanowires are amorphous (i.e. poorly ordered) and the introduction of defects on cycling is not necessarily an issue.

The previous work was truly proof of principal, but unlikely for variety of reasons to be a direct path to commercialization. There's some new work out by a local group that expands on the work of Chen. Fleischeur et al. tried their specialty, glancing angle vapour deposition, to form a thin-film of Silicon composed of many, regular pillars. (Disclosure: our research group collaborates with the group that did this research. I personally do not, however.) In glancing angle deposition, the substrate (onto which the film is deposited) is at nearly right angles to the incoming vapour stream. In thin film deposition, one tends to see small clusters form first due to surface tension. As the clusters grow, they amalgamate together and form a (porous) solid thin film. When the substrate is at high angles of incidence, the first clusters to form shadow any smaller trees and grab more than their fair share of the incoming mass stream. Hence glancing-angle deposition typically forms column-like thin films.

The glancing-angle fabrication method has a number of potential advantages over Chan's technique:

Chan's thin film process relied on a gold catalyst ($$$), whereas the GLAD process only requires a thin layer of chromium for adhesion on Si substrate and none at all on a stainless steel substrate.
Glancing-angle deposition can easily control the spacing of pillars by patterning the substrate.
The glancing-angle films were "robust" when I asked the author about it. He said hitting the batteries with a hammer had no effect on performance, so presumably the pillars were not breaking.
Glancing-angle deposition requires a microscopically smooth surface for proper column formation.

Let's look at some results. The question is, how durable are these anodes compared to graphite? The charge curve is really all we are interested in.

Figure 1: Chan et al. charge capacity after 10 total cycles.
Figure 2: Fleischauer et al. charge capacity after cycling up to cycle 70. I don't recall the reason for the discontinuities but I vaguely recall it had something to do with the test electronics.

Both authors show a very large drop in charge capacity after the first recharge. This means there is some sort of irreversible change to the material occuring from film fabrication to charged and uncharged Si. Then there is a progressive loss in capacity. Evidently Chan and company are less confident in their material as they are only showing results up to ten cycles. Average capacity fade for Fleischeur's battery was found to be 0.3 % per cycle. If we extrapolate, that would imply it would take approximately 750 cycles for the charge capacity of the silicon anode to drop below that of a conventional graphite one. Obviously, that's not good enough for commercial applications.

Overall, I think that this is an important step in terms of fabrication and longevity. We are still looking at a minimum of a decade before any such silicon Li-ion batteries hit the shelves; this is progress on that path.

Poster Boy

2008-12-11T22:13:00.001-07:00

http://online.wsj.com/article/SB122903010173099377.html

Wow.

Oh yeah, GM and Chrysler are bankrupt, just like 80 % of US banks. Piffle.

GM Sales Fall 45 % YoY; Average 31 % Drop

2008-11-03T15:01:00.003-07:00

That's going to leave a mark! USA automobile sales are way way down in October 2008 versus October 2007, as consumer sentiment and credit heads South fast.

About 25 per cent of GM's volume in October 2007 was from leasing, but the auto maker did almost no leasing last month through GMAC, Mr. LaNeve said.

As I mentioned in the comments of this post, when you have to relax your credit requirements to sell cars, you're setting yourself up for trouble in the long-run. I've actually been impressed how well the USA has been holding up under the credit crisis thus far (compared to countries like Iceland, Hungary, Pakistan, etc.) but obviously if the steady drip—drip—drip of job losses continues things will really come to a head. I definitely still stand by my prediction of the US financial sector shrinking in half. The US Treasury bail-outs to date are not solving the trust issue as everyone continues to hoard cash. Tacking on $500 billion a month in federal debt isn't sustainable either.

I'm working towards my doctoral candidacy at the moment so posting will remain sparse until the middle of December.

My Thoughts on the US Election

2008-10-17T16:14:00.003-06:00

Since it's becoming fashionable for energy bloggers (such as Geoffrey Styles and Robert Rapier) to comment on the US election, I thought I would lend my 'formidable' intellect to the debate:

I for one am surprised how many US provinces are polling favourably for the NDP.

Furthermore, I would like to pontificate on one of life's greatest mysteries... Why does the eye perceive the combination of red and blue as purple?

Demand Destruction

2008-10-16T14:45:00.000-06:00

With oil now hovering around $70/bbl, we've seen a decline of roughly 50 % from the peak this year over only a couple of months. I've stated in the past that I felt the run-up starting in February was largely speculation whereas the push from 2002-2007 was more fundemental. Is this new drop an evidence that 2002-2007 was speculation or is it a fundamental move based on supply and demand? I'm going to argue here that this is, once again, a real move, based largely on demand destruction on-going around the world but in particular inside the United States of America.

Oil consumption in the USA started a downhill roll around December last year. In September, it had a Will-E Coyote moment and rolled off a cliff. It's now in free-fall. Oil demand is highly inelastic in the short-term but their is some phase lag that results in more long-term elasticity. What I mean by that is, it takes awhile for individuals and business to adapt to oil price by drilling for more supply, replacing SUVs with econoboxes, driving slower, etc. But when demand drops fast, the price can drop fast too, because supply is short-term inelastic too.

The latest EIA data estimates US petroleum consumption at 18,865,000 bbl/day. Compared to the same time last year, at 21,024,000 bbl/day, that's a drop of just over 10 % yoy. That's a really big deal. From a GDP-to-oil-consumption relation, it suggests the US is headed into a depression. Even during the 1970s oil shocks the US only experienced drops of 3-4 % a year in consumption.

Figure 1: EIA Weekly Oil Consumption (estimate). The chart shows the story: a gradual downturn and then a sudden drop.

That speculative oil bubble that appeared in February? Gone. Yes, Dorthy, a major recession in the country that consumes a quarter of the world's oil can cause a big drop in price. The USA isn't the whole story, but it is driving this price movement.

Figure 2: IEA consumption estimate for OECD countries.

The story starts with the OECD countries, and extends to the BRIC (Brazil-Russia-India-China) 'growing' economies. Consumption was pretty flat from 2005-2007, and then it started dropping in 2008. Note that Figure 2 only extends to August, and the US demand dropped over a million barrels a day in September!

Note when looking at these IEA plots, they are all 12-month moving averages, so any moves you see in the curves likely started a few months earlier. Also note that EIA (US DoE) and IEA (France) data are not strictly equivalent, since they use different methods to come up with their estimates.

Figure 3: IEA Germany and Japan Oil Consumption.

Oil demand in a number of big economies, e.g. Germany and Japan already fell in response to oil prices last year. They are largely unchanged this year, or indeed up. France is already headed back up, as are a number of smaller countries. In North America, Canada's demand is flat and Mexico is well up.

Figure 4: IEA UK and Italy Oil Consumption.

The big weakness in Eurozone oil consumption is coming from Italy, and the UK. However, their drops are still minor in comparison to the story in the `States. If we look over a longer term view, the IEA consumption data (Figure 5) suggest US demand was flat for 2005-2007, so perhaps this recent drop is just the USA making up for lost ground. Looking at US consumption, and world consumption, the two graphs have very similar shapes.

Figure 5: IEA oil consumption data for USA. Future versions of this graph will show a sharp downturn in September.

The BRIC countries are all less transparent. As a consequence of that, releases of their numbers is even slower than OEDC results we see above that are a couple of months behind. In the same manner that the USA drives OEDC and the other countries are just noise, China drives the BRIC numbers. Unfortunately, we don't have any numbers yet on the Olympic effect in China. Vehicle-kilometers in China was probably way down in August, and that's going to have a short term impact on oil demand. China's skies are once again as smoggy as ever before, so unless they've also changed their stockpiling strategy, this is going to have a short-term impact.

Figure 6: China oil consumption (and projections) beside Vehicle Sales in China. Taken from Malcolm Shealy's (Alacrites Inc.) presentation hosted on IEA website.

So outside of a massive step up in China in August and September (which is unlikely) the only other likely variable to examine is oil supply. Production data (Figure 7) indicates supply is actually up this year. This isn't unexpected. It took a couple of years after oil took off in 2002 for the oil companies to get enough confidence to jump into new projects, but a number of projects started in 2003-2004 are now up and running contributing to supply. While the new oil price may choke off new projects, there's still a number in development to stave off the depletion of existing fields.

Figure 7: World oil plus condensates production, 2005-July 2008 (Data from EIA).

So, in conclusion, I think the supply and demand data show pretty conclusively that supply is up, demand is down, hence the price of oil is dropping like a rock. In fact, we have this event occurring at the same time as a commodity is being popped, so the effect is especially strong. This is a good thing. The world economy and the USA in particular is hurting thanks to the bubblicious real-estate fiasco and low energy prices will help conventional economic activities drag us back out of this big hole. I think the housing bust will be extended — adjustable-rate mortgage resets in the US are only about half-way through the pool of potential defaults — and the world economy is not decoupled from the USA so expect fallout damage to hit exporting countries in manufacturing (China, Japan) and commodities (Canada, Russia, Australia) in waves going forward. The US consumer is going to have to live within his or her means, and hopefully revert back to being a citizen first and consumer second.

Can OPEC squeeze the price by implementing quotas? Yes and no. Production of oil products is up big in 2008. There's slack they can take out of the system. Will they? I don't know. OPEC countries in general have not been diversifying their economies so they will have to do something or face the potential for unrest as revenues come back to earth. Basically it comes down to whether or not Saudi Arabia wants to arrest the fall in price, or if Russia as a non-OPEC producer decides to sacrifice some cash flow or not. If I was the Saudi's, I would be thinking about whether or not OPEC as an organization has outlived its usefulness. A Saudi-Russian oil alliance would probably be more practical, and effective.

Looking into the future, it's likely that demand in the USA will be suppressed for awhile, so as a result, investment in new capacity is going to drop especially in conjunction with higher credit rates. Speculative plays in oil shale, gas-to-liquids, and coal-to-liquids are effectively dead. Remember that in order to develop alternative fossil fuels to oil you need to not just cover the marginal cost of production, but also amortize the capital costs, and the capital costs in non-conventional oil are usually very high. I would also expect new deep water plays (Brazil, Atlantic Canada) to come to a grinding halt, but existing ones should go ahead as the cost of production is not excessive.

The most marginal cost-of-production oil in the world is Alberta bitumen, at around $50/bbl. That's not accounting for capital costs at all, which have been in the range of $150,000 /bbl/day capacity recently. Lower than that, and salaries will have to come down to lower costs. Taking that capacity out of the world's supply would only knock off 1.3 million bbl/day. Alberta's provincial government may be facing the end of yet another oil boom with little to show for it.

Banana Republic Bubble Bail-outs

2008-09-29T14:22:00.006-06:00

So, how's that short ban working for you, Mr. Market? I have some further comments to get off my chest with regards to the impetus for this crisis and the attempted bail-out. I see a lot of finger pointing going on but as far as I can tell everyone is doing so from their very own glass house. Let's itemize the combination of failures shall we?

Low interest rates have obviously contributed to the blowing of bubbles. However, general failure of the federal government to provide transparent and even regulation of the financial markets is as big a factor. Part of the problem is that government never reacted to and regulated financial 'innovation', in particular the credit default swaps and options that are now causing a chain-reaction melt-down. The other half of the problem is not enforcing existing regulations particularly in regards to accounting tricks that have allowed insolvent zombie banks to appear to be in the black as they file for bankruptcy or are bought-out. Moves to increase leverage limits haven't helped either.
The financial sector of the US economy has become out-sized relative to the real economy. A symptom of this is the blowing of successive bubbles required to keep such a bloated sector operational. This in turn supported the fraud at the mortgage broker level by creating such a huge demand for bad loans. By historical measures, the financial sector is about twice as big as it should be to fulfill its function of providing credit to business and mortgages to citizens. It is ironic that the financial sector was the biggest proponent of free trade and told manufacturing to suck it up when the race to the bottom was destroying that industry. Now that the underlying base of the US economy has perished and finance is being forced back to reality they are crying for a bail-out. The hypocrisy is deafening; it's your turn to learn about outsourcing.
An excessive concern with status and sense of entitlement amongst the stereotypical consumer-citizen (with the emphasis on consumer). McMansions, Ford Extinctions, granite counter tops, etc. What was the purpose of all this? How did people get fooled into thinking that they needed such things? I believe people are entitled to food, medical care, etc. but such entitlements need to be reigned in to the point that living off the dole isn't anyone's choice. You're not entitled to a 52" plasma-screen TV you purchased with your HELOC.

If these sound like huge, fundamental problems, they are. Around when 'personnel' department became 'human resources' and employees became interchangeable cattle the smart kids stopped going to engineering schools and instead enrolled in law and finance. Unfortunately, financial innovation is a synonym for confidence game. The LCD screen you're looking at? Not finance. The hyperlink? A rare application from the super collider at CERN. In fact I can make a pretty good argument that innovation in the telecommunications industry has stagnated over the last seven years after finance blew it up. I challenge anyone to locate a financial instrument developed in the past 100-years that is necessary to run our modern economy.

The proposed Paulson bail-out was bizarre in that it never even tried to determine which institutions needed to be quarantined. Why the House of Representatives used it as the basis for their counter-proposal I am left without words.

Bank of America, CitiGroup, and JP Morgan Chase have all been busy building the Jenga tower higher (see making the pie higher) in the effort to become too ginormous to fail. Clearly they all expect to be bailed out, which is a pretty amoral way to run a business. "Bail us out or your retirement savings get it!" The appropriate response at this stage is to raise their moral hazard one and audit them, find out that, "Surprize, you're broke!" and nationalize the lot of them temporarily. Cashier the executives, amalgamate the trash from all three and quarantine it, then start breaking them into non-antitrust sized chunks and IPO them off in sequence.

China, Japan, and the sovereign wealth funds are going to get hosed, but they weren't acquiring those assets in order to enrich their own citizens so I'm not going to cry over their spoiled milk. People like to think that these guys are innocent money but I think it's more a matter of the distinction between strategy and tactics. It's likely that this will impair the auction of treasuries at some level but the US needs to tell these currency peggers to get stuffed at some point at time. May as well do it now when you have a good excuse; the US federal government needs to aggressively trim its budget too. 401k's are a tax shelter and hence they really shouldn't have equities/securities in them — they should be a bastion of safety — but they do, so individuals need to be compensated (but not made whole). I think the whole idea of being restricted to picking investments your company's human resources department likes is inane, however.

The D-word

2008-09-16T13:01:00.002-06:00

Hmm... so the price of housing and automobiles has been failing for awhile now. Now that another wave of the credit crisis is causing a commotion, the associated margin calls seem to have deflated the commodities bubble. So are we going to see a general fail in prices everywhere?

Are we now in a deflationary period? I was certainly one who believed that the USA would do anything it could to inflate its debt away. It was the logical strategy given the general level of in-indebtedness at all levels of US society. However, the destruction of rent-seeking capital seems to be pervasive and occurring in massive quantities. The Austrian school certainly says that deflation is exactly what we should expect at the end of a credit-driven bubble. The huge amount of leverage involved and the general cross-connectedness of the Credit Default Swaps (CDS) market seems to make the domino-effect of financial corporation failures unstoppable. In fact, the US Federal Reserve seems to have largely lost control over prevailing interest rates.

This isn't like the old inventory-driven recessions of the past thirty years. Structurally, it looks closest to the run-up to the Great Depression around 1924-29 when all the Austrian banks went down.

Fortunately I don't think we are likely to have another coincidental Dust Bowl event (and farming is not quite as important anymore) to match the horrible times of the Great Depression. However, if the financial sector were to shrink by half, bringing it back in line with historical norms, that would certainly result in a GDP shrinkage of > 10 %, meeting the technical definition for a depression.

Canada isn't going to side-step the fallout on this one. Any large scale demand destruction in the USA will hurt producers up here badly. Stephen Harper was bright to call an election when he did, but he would be well advised not to stick his head in the sand. The USA is inevitably going to become more mercantilist so let's move to get ahead of that, shall we?

I continue to believe that the way out of this mess is a drive to shift the developed economies of the world away from fossil fuels and into renewable sources of electricity. Any such drive would generate a lot of high-quality jobs, present many R&D opportunities for the productive employment of capital, and achieve some enormous environmental and security side benefits.

Nanoparticle LiFePO4 Batteries

2008-09-03T15:11:00.003-06:00

The lithium-ion batteries based on phospho-olivine (i.e. LiMPO₄, where M = {Mn,Co,Fe}) crystalline structure have been the subject of a great deal of research over the past decade. A recent paper in Nature Materials from Gibot et al. has demonstrated some of the developments in the area and I'd like to rehash them here [1]. The paper demonstrates fabrication of a single phase LiFePO₄ with very small particle dimensions. It's not an, "Oh my god what an amazing engineering development paper," but rather one of scientific interest to elucidate the difference between two-phase and single-phase Li-ion batteries.

LiFePO₄ thus far seems to be the most impressive performer, especially from a safety perspective. It is produced entirely in solution (e.g. a beaker) by a chemical recipe. I don't know what the yields are like but the nature of the production method implies that it can be undertaken in large vats on an industrial scale.

Unfortunately, it suffers from poor conductivity characteristics. Two main approaches have been made to improve the conductivity of LiFePO₄: (1) to coat the particles with a thin layer of amorphous carbon, and (2) to manufacture the LiFePO₄ in the form of small nanoparticles (~ 40 nm average axial dimension). Of course, both approachs can be combined.

Adding carbon improves the conductivity but adds an, "electrochemically inactive," layer to the cathode material, hence reducing performance by adding dead weight to the battery. One can imagine that when you take a mass of Li-ion particles and sinter them together to form the cathode, if they've all been coated with carbon then there's an electronically conductive pathway from any buried particle to the electrolyte.

For the nanoparticle approach, presumably the higher ratio of surface area to volume reduces the ion diffusion length, but the literature also suggests that the introduction of defects to the nanoparticles may also improve conductivity. I know from experience that stacking faults (such as twins) can act as diffusion pathways for reaction species in solid-state reactions.

Normally the cathode material is really Li_xFePO₄, where x = 0.5 - 0.75. This is (at least partially) as a result of the boundry between crystallites being composed of an extremely lithium poor phase (x ~ 0.03). The primary advance shown in the Gibot paper is that they made the nanoparticles small enough that only a single phase is found in each particle. To explain, if you are familar with the difference between monocrystalline and polycrystalline silicon solar cells, the sub-40 nm LiFePO₄ nanoparticles are monocrystalline. Particles in the range of 100 nm are polycrystalline and hence have the low lithium phases present at the boundaries of each crystallite. Note that there's no fundamental electrochemical advantage to the monocrystalline approach as far as I know.

Figure 1: Potential-capacity and capacity-power curves for nanoparticle LiFePO₄(reprinted from [1]). In the top figure, 'C' represents a charge curve and 'D' a discharge curve for carbon-coated LiFePO₄ nanoparticles. The number after the letter is the number of hours the discharge took place over. I assume '2D' is the discharge curve for thirty minutes.

I infer from the paper that a big difference here seems to be in the lithium loading. Gibot showed by a variety of methods that their nanoparticle was loaded with more lithium (x = 0.82-0.92). However, their discharge performance curves aren't actually more impressive than existing LiFePO₄ batteries with larger particles. Existing batteries have flatter discharge curves from what I've seen.

The real advantage for these monocrystalline nano-LiFePO₄ is likely to be reversibility. As I've discussed previously, the volume of the crystal changes from lithuim insertion to deinsertion. This introduces strain into the crystal and after many cycles defects will form and degrade performance. However, in a monocrystalline material there's not a lot to break. The nano-LiFePO₄ does have some substitution defects (Fe where Li should be and vice versa) but without the crystal boundries the defect density is likely to be lower overall.

Another potential advantage for the nanoparticle approach is that it requires less in the way of process temperature (108 °C versus 500 °C over 24 hours) compared to the traditional approach. That should make the manufacturing process less energy intensive and less expensive.

[1] P. Gibot et al., "Room-temperature single-phase Li insertion/extraction in nanoscale LixFePO4", Nature Mat 7 (2008), 741-747.

On the Topic of That Oil Bubble

2008-08-21T13:08:00.002-06:00

About that oil bubble I was talking about a few months ago:

One trader held 11% of Nymex oil contracts: report

Hmmm...

I find it hilarious that almost all the big-wig economists around were proclaiming their was no bubble (e.g. Krugman, JDH). I think it was pretty obvious, as soon as NY.MEX futures volume exploded in February 2008 and the successively forward price of oil futures switched to all increasing rather than decreasing (as it was 2002-2007) that we were seeing some serious speculation games.