Archive for the ‘Science’ Category

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Fluoridated drinking water: public-health triumph, or force-fed meds?

November 29, 2016

In general, I trust our government. I trust it to use my taxes wisely, protect the less fortunate among us, and enact policies based on sound research and reasoning.

If scientists from the government tell me that the scientific consensus is such-and-such, I generally believe them. Sample topics: climate change, vaccines, evolution.

Thus, when I heard that citizens’ groups were opposing the fluoridation of public drinking water, in contrast to the official position of the Centers for Disease Control and Prevention (CDC), I was initially skeptical. It sounded like a variation on the tragically misguided “vaccines are dangerous” movement.

But now that I’ve done some more reading and thinking about fluoridation, I think the anti-government fringe groups might be right!

Admittedly, a few hours of reading does not make me an expert on fluoridation. (So far, I’ve looked at the websites of the American Dental Association [ADA], CDC, Fluoride Action Network [FAN], and Rutland Fluoride Action, and followed links from these sites to other files such as the National Research Council’s 2006 report on fluoride in drinking water.) But, as someone with a Ph.D. in Physiology & Biophysics plus 14 years of postdoctoral research and teaching experience, I am qualified to comment on the issue.

It’s a challenging issue to tackle because there is a huge body of research on the biological effects of fluoride, which the two sides filter quite differently. For example, a thorough 2015 meta-analysis of the issue conducted by the independent, rigorous Cochrane Database group is touted by the FAN as showing “no valid evidence exists to prove fluoridation works,” while the ADA and CDC complain that the Cochrane analysis excluded valid studies that indicate benefits of fluoridation.

It’s hard for a neutral, semi-informed observer to know what to make of such debates.

Still, amidst the fog of disputed data and accusations of bias, the anti-fluoridation crowd does have a simple argument that I find compelling. Here it is:

1. Fluoride is a drug, not a nutrient.

2. Mass-administering a drug to entire communities, without individuals’ consent, can only be justified if we are extremely confident that the benefits-to-risks ratio is extremely high.

3. The available evidence does not warrant such extreme confidence.

Of these, claim #1 may be the most contentious. The ADA seems to disagree, as its 5 Reasons Why Fluoride in Water is Good for Communities include “It’s natural.”

“Fluoride is naturally present in groundwater and the oceans,” the ADA reassures us. Well, yes — but so is uranium-238. Should we be adding that to our water too?

The ADA continues, “[Fluoridation of water is] similar to fortifying other foods and beverages, like fortifying salt with iodine, milk with vitamin D, orange juice with calcium and bread with folic acid.”

The FAN rebuts this effectively.

It is now well established that fluoride is not an essential nutrient. This means that no human disease -– including tooth decay -– will result from a “deficiency” of fluoride. Fluoridating water supplies is therefore different than adding iodine to salt. Unlike fluoride, iodine is an essential nutrient (the body needs iodine to ensure the proper functioning of the thyroid gland). No such necessity exists for fluoride.

If fluoride is not a nutrient, then what is it? I find the FAN’s stance completely reasonable:

All water treatment chemicals, with the exception of fluoride, are added to make drinking water safe and pleasant to consume. Fluoride is the only chemical added to treat people who consume the water, rather than the water itself. Fluoridating water supplies can thus fairly be described as a form of mass medication, which is why most European countries have rejected the practice.

This classification of fluoride as a drug is consistent with official definitions from the Food and Drug Administration (FDA).

People usually are prescribed specific dosages of drugs according to their age, weight, medical history, etc. For fluoride in water, however, doses will vary wildly, not based on individuals’ “needs,” but based on how thirsty they are. It’s a bit unsettling, at the least.

Claim #2 concerns informed consent. I have some relevant professional experience, having conducted laboratory research and educational research that required approval from my university’s Institutional Review Board (IRB) as well as the consent of the research subjects themselves.

It’s a lot of tedious paperwork. In my own proposals, for example, I’ve spent many paragraphs explaining why students will not be harmed if they anonymously complete a survey, and guaranteeing that the students can nonetheless skip the survey, without being punished, if they have any objections to it. Still, I’m grateful that my institution has a serious review process that reflects its firm commitment to respecting individuals’ autonomy. This respect is a bedrock value of civilized society in general, and infringements upon it must be well-justified.

So is it OK to force-feed a drug to populations at haphazard levels related to individuals’ thirst? Sure — but only if the drug has obvious, important benefits and is extremely safe.

So — claim #3 — what does the evidence look like for benefits and risks?

Regarding benefits, the above-mentioned Cochrane study basically says that there IS evidence that fluoridated water reduces tooth decay, but that this evidence is not nearly as strong as we would like.

Regarding risks, the above-mentioned NRC report devotes over 200 pages to reviewing fluoride’s effects on the musculoskeletal, reproductive, nervous, endocrine, digestive, renal, and immune systems. For most of these systems, the NRC concluded that more research was needed, which is not particularly helpful because scientists always say that about everything (thus justifying our existence).

Still, based on data showing that high fluoride levels can compromise teeth and bones, the NRC concluded that the Maximum Level Contaminant Goal (MLCG) be altered downward from the previously established standard of 4 milligrams per liter (mg/L). More recently, the Department of Health and Human Services (HHS) has lowered its recommended level of fluoride in the water to 0.7 mg/L (down from a previous recommended range of 0.7-1.2 mg/L). These changes can be taken as an acknowledgment by experts that greater caution regarding fluoride exposure is warranted. Throw in some journal articles and government grant proposals that have made it through the peer review process, and you don’t need to be a conspiracy theorist to think that mass fluoridation has been enacted prematurely.

In a subsequent post, I will address the issue of “topical” versus “systemic” delivery of fluoride.

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Crowther & Crowther (2015)

June 24, 2015

Two recently completed collaborations with my 8-year-old son:

1. Green revolution: salad spinning superseded. Bricolage 33: 110-112, 2015.

2. STEM songs: not just child’s play (display case installation, Discovery Hall, UW-Bothell)

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More mandatory fun

September 25, 2014

As a follow-up to the summer’s odd teaching slides, here are some new examples fresh from this fall’s Anatomy & Physiology course (BIOL 241).

Dr. Alfred Yankovic, Adjunct Professor of Medicine

Red Rover: the nano version

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Stephen, Be Heard!

September 14, 2014

The Dynamic Ecology and Phylogenomics blogs drew my attention to a new “must-read” article: On whimsy, jokes, and beauty: can scientific writing be enjoyed? by Stephen B. Heard (Ideas in Ecology and Evolution 7:64-72, 2014). The abstract is below.

While scientists are often exhorted to write better, it isn’t entirely obvious what “better” means. It’s uncontroversial that good scientific writing is clear, with the reader’s understanding as effortless as possible. Unsettled, and largely undiscussed, is the question of whether our goal of clarity precludes us from making our writing enjoyable by incorporating touches of whimsy, humanity, humour, and beauty. I offer examples of scientific writing that offers pleasure, drawing from ecology and evolution and from other natural sciences, and I argue that enjoyable writing can help recruit readers to a paper and retain them as they read. I document resistance to this idea in the scientific community, and consider the objections (well grounded and not) that may lie behind this resistance. I close by recommending that we include touches of whimsy and beauty in our own writing, and also that we work to encourage such touches in the writing of others.

To this nicely argued piece, I just want to add a few examples of indifference or hostility to my own attempts at whimsy, humor, and/or beauty.

(1) My grant proposals to the NWRCE and PNWRCE, 2010.

Striving to keep readers with me through the Conclusion section, I wrote:

We believe strongly in the importance of the central goal of this proposal, i.e., linking antibacterial compounds to Burkholderia proteins in a manner that will facilitate validation of new drug targets. This interest in compound-target links is not simply a fetish of the investigators involved in this project; within some pharmaceutical firms, knowing the target of a compound with activity against cells is considered absolutely vital for progressing compounds to leads.

A colleague discouraged me from using the word “fetish” on the grounds that “it reminds me of foot fetishes.” Perhaps she was right, but I kept it in as a tiny rebellion against unrelenting formality.

The proposals were rejected.

(2) G.J. Crowther et al., Identification of attractive drug targets in neglected-disease pathogens using an in silico approach, PLoS Neglected Tropical Diseases 4(8): e804, 2010.

This paper contained numerous lists of possible drug targets. Since one of the pathogens covered was Leishmania (the cause of leishmaniasis), the paper was known internally as the “Listmania paper” throughout 10 months of writing and revising. Meanwhile, we searched and searched for a compelling title distinct from that of our first paper on the same topic … while carefully avoiding the most interesting and evocative bit that we had come up with — i.e., the word Listmania. A coauthor killed the term by arguing, reasonably enough, that a pun about a pathogen might be insensitive to the pathogen’s victims. But a “catchier,” less cautious title might also have raised leishmania awareness more effectively.

(3) G.J. Crowther, The SingAboutScience.org database: an educational resource for instructors and students, Biochemistry and Molecular Biology Education 40(1): 19-22, 2012.

The submitted manuscript included this:

The total manpower behind this website, rounded to the nearest whole number of FTE’s, is 0, so its maintenance is kept relatively simple.

Once the journal’s copy editor got ahold of it, it became:

The total manpower behind this website, rounded to the nearest whole number of Full-Time Equivalents (FTE’s), is 0, so its maintenance is kept relatively simple.

To me, this change reduced the sentence’s rhetorical punch and humor. Yet the edited version was (slightly) clearer, and I knew better than to argue for style over clarity. I reluctantly accepted the edit.

(4) G.J. Crowther et al., A mechanism-based whole-cell screening assay to identify inhibitors of protein export in Escherichia coli by the Sec pathway, Journal of Biomolecular Screening 17: 535-41, 2012.

Our submitted manuscript included the following:

While previous studies had included beta-mercaptoethanol in assay buffers, presumably to maintain cytoplasmic beta-gal in a reduced and active state, it did not appear necessary to preserve beta-gal function under our assay conditions; EC626’s response to maltose was similar with and without beta-mercaptoethanol (Fig. 3). Thus, in performing this assay, the unpleasant odor of beta-mercaptoethanol may be avoided.

A reviewer wrote, “The sentence which includes ‘the unpleasant odor of beta-mercaptoethanol’ is not appropriate.”

Here was another chance to stand up for ever-so-slightly-less-orthodox, ever-so-slightly-less-dry writing. This time I stood my ground and got my way.

“We respectfully disagree,” I responded. “It is a minor point, but the omission of beta-mercaptoethanol provided much relief to the rest of our lab, and this is worth noting.”

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More juxtapositions

July 18, 2014

I have a soft spot for oddly juxtaposed teaching materials, e.g., a handout covering both lab-grown meat and the structure of the song “Hound Dog.”

Here are some strange bedfellows that appeared in animal physiology this spring and summer.

2014_06_24_sodium_gradient_border

Above: two ways to convey the idea that most sodium ions (chemical symbol Na+) is outside cells rather than inside.

2014_07_17_Botox_border
Above: Clostridium botulinum toxin, an inhibitor of the salt glands of marine birds … and the facial muscles of wealthy humans.

2014_05_20_Goldilocks_border
Above: In retrospect, this illustration of the importance of blood pressure regulation may have been too oblique.

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The neurobiology of celebrity worship

July 8, 2014

The 5th edition of Biological Science by Scott Freeman et al. includes the following figure.
The Jennifer Aniston neuron.

Summarizing the study (R.Q. Quiroga et al., Nature 435: 1102-7, 2005) on which this figure was based, the textbook says, “Through experience, at least one of this patient’s neurons became singularly devoted to the concept of Jennifer Aniston.”

With this example, the textbook authors raise the issue of whether memories are stored in specific neurons rather than in distributed networks.

Are they are also implying that we collectively devote too many neurons to Jennifer Aniston and not enough to, say, Rita Levi-Montalcini?

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Reminder: correlation is not causality

February 27, 2014

A research study by Martin Hoffman and Eswar Krishnan concludes, “Compared with the general population, ultramarathon runners appear healthier and report fewer missed work or school days due to illness or injury.”

The March 2014 issue of my local running magazine summarizes this study as follows: “Keep logging those miles, ultrarunners! Your body will thank you for it in the long run.”

See the difference?

The study itself simply notes that ultramarathoners are, by most measures, healthier than normal. The running magazine leaps (or perhaps sprints) to the conclusion that these runners’ training is what keeps them so healthy. But we can’t rule out the opposite: maybe these people’s good health is what allows them to run so much; maybe their impressive mileage tallies are an effect, rather than a cause, of their good health. Or maybe the ultrarunners surveyed differ from the general population in other ways, unrelated to running, that account for their superior health.

Numerous studies have provided strong evidence that running promotes good health, but this study isn’t one of them.

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The wisdom of crowds?

February 9, 2014

From the Seattle Times: 700,000 at Seahawks parade? Doesn’t add up, experts say.

It’s a lighthearted article, but it touches on the methodology of crowd estimation and uses some basic math to show that the number of parade attendees was less than the official estimate of 700,000.

How did readers respond to this dollop of evidence-based analysis? There were several themes, as exemplified by the following online quotes. (My interpretations are in brackets.)

(1) Semians: “Quit trying to overanalyze everything and simply live in the moment.” [We shouldn’t care about this information.]

(2) picklesp: “It sure as heck felt like 700,000 from ground level.” [This information doesn’t match my personal experience.]

(3) Peterkirk: “These guys are just trying to rain on our parade for whatever reason, and well tough, it didn’t rain on the parade on Wednesday and your diatribe (reporting?) isn’t going to make it rain today.” [This information doesn’t make me feel good, so I’ll ignore it.]

(4) Mr. Mytzlplk: “The ‘experts’ vary by 200,000 in their ‘real analysis.’ The fact that they’re so far off from each other tells me that they don’t know what they’re doing.” [Experts disagree about the details, so their analyses are worthless.]

(5) picklesp: “Experts get paid to pontificate.” [Experts have their own biases and agendas — which is true.]

(6) gloryhound: “I’m also skeptical of these two ‘experts” qualifications.” [The “experts” aren’t really experts.]

The above excerpts are from some of readers’ HIGHEST-rated comments. Here are two of the LOWEST-rated ones:

[from dawgsage:]

Actually 2.5 sq. ft /person is a square of almost 19 inches per side. Measuring the width of my body without a coat shows approximately 19 inches shoulder to shoulder, with a coat let’s add an inch making it 20 inches. A 2.5 square foot rectangle, with one side 20 inches would then require the other side to be 16.2 inches, from front to back. Conservatively, my measurement is 10 inches front to back. This means there would be 6.2 inches forward from my front to the back of the body of the person in front, and 6.2 inches in the back of me to the body of the next person, while laterally I am shoulder to shoulder to the adjacent people. So no I do not think it is not like standing in line, you really can’t get more crowded than that unless you were in an Iraqi prison under Saddam. So I believe the basis of the low estimates are credible.

[from CO Dawg:]

Rather than just say “well I don’t believe you!” to the experts, just do this simple experiment: put on a winter jacket (remember, it was cold that day) and stand against the wall with your arms against your side, then have someone mark the wall with chalk at your elbows. Measure that width. Then turn sideways and mark again the two widest points (belly and bottom for me, your points may vary). Measure that width.

Now, grab a calculator and multiply your personal width by personal depth. That is the square footage of space you occupy if you were standing in a crowd elbow to elbow belly to back and back to belly, like at a rock concert, and represents a good indication of the maximum crowd density at the parade.

When i did this with a sweatshirt on i came up with 2.1 feet wide and 1.25 feet deep, for 2.65 square feet, a little above the minimum cited. However, if i put on a winter jacket it adds an inch to all four sides so the measurements jump up to 2.25 by 1.42 feet, or 3.2 square feet. Adding just one more inch to each measurement increases my footprint to 3.8 square feet, and adding 3 inches increases it to 4.7 square feet. I wont presume anything about your personal space requirements, but when someone is 3 inches away from me, i still feel pretty crowded. I can thus conclude that the experts have presented a reasonable range for each person’s footprint

I have no means to measure the overall footprint of the crowd along the route, but had they asked me to do crowd estimates i would have employed the same methodology they use (measurements from an aerial photo), and probably would have come up with numbers similar to their’s. I would have multiplied the overall crowd foot print by an average space per person of 3.5 square feet (generally splitting the difference between my numbers), added 15% to account for people standing outside the footprint or watching from offices, and likely come up with a forecast of somewhere between 350-400k. Which is still a heck of a crowd.

And for those of you dismissing my opinion because of my location, we’re not immune to overly enthusiastic crowd estimates in Denver, too. I was at a presidential campaign speech in Civic Park that supposedly was attended by 100,000 people, and didnt even need to do the math to know that estimate was comically high.

So, to summarize: dismissal of the information for any old reason? Thumbs up! Attempts to check the math and verify its reasonableness? Thumbs down!

While no legislation hinges on this particular estimate, I’m troubled by the attitudes displayed here, i.e., limited interest in the nuances of data and relevant expertise. I submit that, in other arenas, this limited interest has led to the popularity of positions like “evolution is just a theory,” “vaccines cause autism,” “global warming is a hoax,” and “animal testing is unnecessary.”

In response, we scientists can grumpily bemoan an incurious public … or we can recognize that facts alone don’t always move the needle of public opinion, and we can get better at appealing to people’s emotions and imaginations.

comments from a data denialist

do the math!

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Calculations of bees’ impact on strawberries’ market value

January 16, 2014

In the course I’m currently teaching, we’ve been reading the paper Bee pollination improves crop quality, shelf life and commercial value by Bjorn K. Klatt et al.

As explained nicely by Erik Stokstad, the paper documents how strawberries benefit from pollination by bees, as opposed to pollination by wind or self-fertilization. It turns out that, on average, bee-pollinated strawberries are larger than others and also have fewer odd shapes, better color, and superior firmness. This detailed look at strawberry quality is a useful extension of past studies showing that insect pollination often boosts crop quantity (i.e., yield).

In making their case for the agricultural importance of bees, Klatt et al. say that bee pollination accounts for at least $1.44 billion of the value of the $2.90 billion strawberry market in the European Union (EU). While I accept the take-home message that bees add a lot of value, I sure wish the authors had explained their calculations better.

The $1.44 billion estimate is the sum of two factors: $1.12 billion in market value of the fresh berries, and another $0.32 billion corresponding to improved shelf life. Let’s consider each of these in turn.

The figure of $1.12 billion is introduced in this section of the Results:

Bee pollination resulted in strawberry fruits with the highest commercial value (figure 1a). On average, bee pollination increased the commercial value per fruit by 38.6% compared with wind pollination and by 54.3% compared with self-pollination. Fruits resulting from wind pollination had a 25.5% higher market value than self-pollinated fruits. Pollination treatments were stronger than differences between varieties and thus had a main effect across all varieties (see table 2 for AICc and likelihood values). Our results suggest that altogether, bee pollination contributed 1.12 billion US$ to a total of 2.90 billion US$ made with commercial selling of 1.5 million tonnes of strawberries in the EU in 2009 [1]—but so far without consideration of the monetary value provided by enhanced shelf life (see below).

Figure 1 indicates that the mean value of 1000 wind-pollinated berries was ~$13.80 and the mean value of 1000 bee-pollinated berries was ~$22.40. The value of the wind-pollinated berries thus represents a ~38.6% DECREASE in value relative to the bee-pollinated berries; alternatively, the value of the bee-pollinated berries is a 62.9% INCREASE over the value of the wind-pollinated ones. A 62.9% increase takes us from $1.78 billion (the hypothetical value of strawberries only pollinated by wind) up to $2.9 billion, giving us the reported $1.12 billion boost from bees. The authors’ mention of a 38.6% increase when they meant a 38.6% decrease is not exactly a big deal, but initially made their math baffling to me and my students.

Perhaps more significantly, the reported market values reflect the classification of strawberries into commercial grades by the first author. Ideally, the first author would have rated the berries while “blinded,” i.e., without knowing which ones came from which treatments (bees, wind, or self). The paper doesn’t mention blinding, so I fear that there was the potential for a pro-bee bias.

Now for the $0.32 billion due to improved shelf life:

Bee pollination strongly impacted the shelf life of strawberries by improving their firmness (figure 2a). The firmness values of each treatment and variety were related to shelf life, measured as the number of days until 50% of fruits had been lost owing to surface and fungal decay (see the electronic supplementary material, S3). Higher firmness resulting from bee pollination potentially elongated the shelf life of strawberry fruits by about 12 h compared with wind pollination, and by more than 26 h compared with self-pollination. After 4 days in storage, only 29.4% of the wind-pollinated fruits and none self-pollinated fruit were still marketable, whereas, at the same time, 40.4% of the bee-pollinated fruits remained in a marketable condition. Thus, bee pollination accounted for a decrease of at least 11.0% in fruit losses during storage. These findings suggest that the value for bee pollination calculated in section 3a(i) has to be increased to accommodate this impact on the shelf life of strawberries. Hence, pollination benefits on the shelf life of strawberries potentially added another 0.32 billion US$ to the commercial value of strawberry pollination.

Here it’s clear that the authors got $0.32 billion by multiplying 11% by $2.9 billion. What’s less clear is the meaning of “storage” (did the unspecified storage conditions simulate those typically used by strawberry farmers/distributors/vendors?) and the reason(s) why a duration of 4 days was used in this calculation (is this a typical time between harvesting and consumers’ purchases?).

Such details aside, here’s a more general question relevant to both components of the $1.44 billion estimate. To what extent are commercial strawberries pollinated by bees in the wild?

The calculations assumes that the study site — a field in Germany — is representative of most or all commercial strawberry farms in Europe. The study site was intentionally set up near well-established bee hives and nests; are most or all European strawberry farms situated similarly? Perhaps the answer is obvious to people with relevant expertise, but the paper doesn’t say. It’s worth noting that if only half of commercial strawberry fields enjoy bee pollination, the estimates of bees’ economic impact would need to be cut in half.

Considering that the paper trumpets a billion-dollar claim in its abstract, more information on the calculations underlying that claim would have been appropriate. At least that’s how I see it — comments from real ecologists (Jeremy?), as well as others, are welcome!

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Civil discourse

December 30, 2013

A recent, typically excellent post at Dynamic Ecology addressed the question of “How do you critique the published literature without looking like a jerk?”

While I like Brian and Jeremy’s suggestions, they don’t capture the extent to which perceptions of jerkiness depend on very specific choices in wording, rhetorical structure, etc. I want to emphasize here that small changes can make a big difference in how you are perceived.

Brian and Jeremy did provide the following language/writing tips (paraphrased by me):

1. Don’t make ad hominem attacks.

2. When possible, identify possible solutions to the problems you’ve identified.

3. Don’t heap too much scorn upon one individual paper or scientist if the problem is common to multiple sources.

4. Focus on facts rather than opinions.

To these, I add the following additional pointers for avoiding the label of “jerk.” (Some were taken from A guide for new referees in theoretical computer science by Ian Parberry, which I consider relevant because standards for pre- and post-publication review should be similar.)

5. Define the viewpoint from which you conducted your evaluation. What do you know about and care about? What do you NOT know about or care about? Confess possible biases.

6. Acknowledge the positive aspects of what was done.

7. Be as specific as possible in your criticisms. Statements like “the data in Figure 5 were misinterpreted” are both more justifiable and less catty than “this study adds nothing to the field.” If you are questioning one particular paper, consider your target to be the paper rather than the scientist(s) who wrote it. “What’s wrong with this paper?” is usually a reasonable question to ask, but “what’s wrong with these scientists?” often registers on the jerk-o-meter. Also be specific in providing references. Claiming support from unspecified sources is sloppy and rude, but even incomplete citations such as “Johnson 2012” may be more ambiguous than helpful.

8. Give the most space to the most important problems. Don’t dwell on minor flaws. Harping on spelling errors makes you seem like a jerk.

9. Avoid unnecessarily dramatic language. In a manuscript review, I once identified four problems as “critical flaws.” A colleague noted that my concerns would be just as clear if I used a softer phrase such as “main flaws.”

In compiling this advice, I became curious as to how well I follow it, so I rated my past critiques of Lore of Running by Timothy Noakes, Born to Run (part 1; part 2) by Christopher McDougall, “Metabolic Factors Limiting Performance in Marathon Runners” by Benjamin Rapoport, Wheat Belly by William Davis, and “Misconceptions Are So Yesterday!” by April Maskiewicz and Jennifer Lineback. Results are below.

self-critique of my critiques

By my own reckoning, I’m not a complete hypocrite, but there certainly is room for improvement.