Antifragile: Things That Gain from Disorder (91 page)

Note that the concern of this author is not evidence, but rather absence of it and how researchers manage such a problem. The focus is in detecting missed convexities.

Effectiveness of low-calorie sweeteners:
One gets plenty of information by looking at studies by defenders with vested interests. De la Hunty et al. (2006) shows “advantages” to aspartame, with a meta-analysis, but focusing on the calorie-in calorie-out method, not overall weight gains. But reading it closely uncovers that the core is missing: “Some compensation for the substituted energy occurs but this is only about one-third of the energy replaced and is
probably
[emphasis mine]
less than when using soft drinks sweetened with aspartame. Nevertheless these compensation values are derived from short-term studies.” Obviously, the paper was financed by a maker of aspartame. A better study, Anderson et al. (2012), though marred with conflict of interest (authors’ support from food companies), concludes: “there is no evidence that LCS (low calorie sweeteners) can be claimed to be a cause of higher body weight in adults. Similarly evidence supporting a role in weight management is lacking.” The last sentence is the only one that I can pay attention to as it is evidence “against interest.” Had there been benefits, we would have known about them. In other words, we are incurring iatrogenics of these sweets-without-calories without evidence, as of 2012, that they even work!

Mithridatization and hormesis:
In Pliny, Kaiser (2003), Rattan (2008), Calabrese and Baldwin (2002, 2003a, 2003b). Note that they miss the convexity argument or the insight about the departure from the norm—hormesis might just be reinstatement of normalcy.

Fasting and hormesis:
Martin, Mattson et al. (2006). Cancer treatment and fasting, Longo et al. (2008), Safdie et al. (2009), Raffaghelo et al. (2010)); on yeast and longevity under restriction, Fabrizio et al. (2001); SIRT1, Longo et al. (2006), Michan et al. (2010); review work in Blagosklonny et al. (2010).

Definition of hormesis:
Mattson (2008) for local definition, Danchin et al. (2011) for more complex-systems approach.

Aging, longevity, and hormesis:
An extremely rich research; Radak et al. (2005), Rattan (2008), Cypster and Johnson (2002) for the C-elegans; Gems and Partridge (2008), Haylick (2001), Masoro (1998), Parsons (2000); for inflammation and Alzheimer’s, Finch et al. (2001).

Bone density and load:
Dook (1997) for females, Andreoli et al. (2001) for more general athletes; Scott, Khan, et al. (2008) for general exercise. Aging for females: Solomon (1997), Rautava et al. (2007); Conroy et al. (1993) for young females.

Bone density and bicycle riding:
Nichols et al. (2003), Barry et al. (2008).

Bone density and Olympic-style weightlifting:
Some “weightlifting” studies mistake the resistance exercise on machines for real naturalistic weightlifting that stresses the skeleton. Conroy et al. (1993) is a more ecologically robust study because it focuses on weight.

Thyroid:
Earle (1975).

Cholesterol:
Non-naive look, Scanu and Edelstein (2008).

Lewontin and life expectancy:
Lewontin (1993). Got idea for the potential unreliability of the Lewontin estimation and was directed to the CDC data from some article on the Web I can’t remember.

Outdoors not sports:
Rose et al. (2008). Higher levels of total time spent outdoors, rather than at sports per se, were associated with less myopia and a more hyperopic mean refraction, after adjusting for near work, parental myopia, and ethnicity.

“Neurobabble,” “brain porn” studies:
Weisberg (2008), McCabe (2008), also “neuroscience and the law,” report by the U.K. Royal Society. Note that the writer Jonah Lehrer used brain porn quite effectively, building a narrative using some loose brain story, playing the narrative fallacy to the hilt—until he was caught creating both narrative and data to back it up.

The pressure on dentists to generate revenues:
“Dental Abuse Seen Driven by Private Equity Investments,” Sydney P. Freedberg, Bloomberg News, May 17, 2012.

Significance:
Simply, people in social science should not be using statistics any more than an accountant should be given a surgeon’s knife. The problem of misunderstanding significance affects professionals. See McCloskey and Ziliak (1996),
Ziliak and McCloskey (2008), Soyer and Hogarth (2011), Kahneman and Tversky (1971), Taleb and Goldstein (2012).

Practitioners and theoreticians in mathematical finance failing to understand an elementary notion in statistics in spite of all the hype:
Evidence in Taleb and Goldstein (2007).

Missing nonlinearities of dose response:
The case of radiation is rather stark, Neumaier et al. (2012). “The standard model currently in use applies a linear scale, extrapolating cancer risk from high doses to low doses of ionizing radiation. However, our discovery of DSB clustering over such large distances casts considerable doubts on the general assumption that risk to ionizing radiation is proportional to dose, and instead provides a mechanism that could more accurately address risk dose dependency of ionizing radiation.” Radiation hormesis is the idea that low-level radiation causes hormetic overreaction with protective effects. Also see Aurengo (2005).

Statins and convexity:
For instance, with statin drugs routinely prescribed to lower blood lipids, although the result is statistically significant for a certain class of people, the effect is minor. “High-risk men aged 30–69 years should be advised that about 50 patients need to be treated for 5 years to prevent one [cardiovascular] event” (Abramson and Wright, 2007).

Statins side effects and (more or less) hidden risks:
Side effects in musculoskeletal harm or just pain, Women, Speed et al. (2012). General assessment, Hilton-Jones (2009), Hu Chung et al. (2012). Roberts (2012) shows another aspect of convexity of benefits, hence harm in marginal cases. Fernandez et al. (2011) shows where clinical trials do not reflect myopathy risks. Blaha et al. (2012) shows “increased risks for healthy patients.” Also, Reedberg and Katz (2012); Hamazaki et al.: “The absolute effect of statins on all-cause mortality is rather small, if any.”

Harlan Krumholz,
Forbes,
April 29, 2011:

Problem is that drugs that improve blood test results may not lower risk. For example, many drugs that reduce LDL or raise HDL or lower blood sugar or blood pressure, do not, against all expectations, lower risk—and in some cases they increase risk.

This is particularly true when considering treatment options to prevent a future event such as a heart attack. Unfortunately, for many drugs that affect risk factors, studies that investigate whether patients benefit are either not done or delayed. This is the case with ezetimibe, a Merck agent that reduces LDL. Because the study that will include information about patient outcomes will only be completed when ezetimibe comes off patent, we will not know how it actually affects risk for a few more years. This billion dollar drug’s approval and sales have been solely based on its effect on a blood test.

For the fibrates, though, we are more fortunate. There are studies of patient outcomes, and fenofibrate, the Abbott drug, has been tested twice in large studies. In both, the drug failed to reduce the risk of the patients taking it even as it very effectively lowered their triglyceride levels. Most recently, in a $300 million trial by the National Institutes of Health, no benefit was shown for the Abbott drug when it was combined with a statin—compounded by a suggested harm for women. The former concern is sufficiently high to have prompted the FDA to convene an advisory committee to review the findings.

Back:
McGill (2007); iatrogenics surgery or epidural, Hadler (2009), Sayre (2010).

Doctor’s strikes:
There have been a few episodes of hospital strikes, leading to the cancellation of elective surgeries but not emergency-related services. The data
are not ample, but can give us insights if interpreted in
via negativa
mode. Extracting the effect of elective surgery, Argeseanu et al. (2008).

Diabetes and pharmacological treatments (ACCORD study):
The ACCORD study (Action to Control Cardiovascular Risk in Diabetes) found no gain from lowering blood glucose, or other metrics—it may be more opaque than a simple glucose problem remedied by pharmacological means. Synthesis, Skyler et al. (2009), old methods, Westman and Vernon (2008).

Discussions of diabetes and diet:
Taylor (2008), reversal in Lim et al. (2011), Boucher et al. (2004), Shimakuru et al. (2010); diabetes management by diet alone, early insights in Wilson et al. (1980). Couzin, “Deaths in Diabetes Trial Challenge a Long-Held Theory,”
Science
15 (February 2008): 884–885. Diabetes reversal and bariatric (or other) surgery: Pories (1995), Guidone et al. (2006), Rubino et al. 2006.

Autophagy for cancer:
Kondo et al. (2005).

Autophagy (general):
Danchin et al. (2011), Congcong et al. (2012).

Jensen’s inequality in medicine and workout:
Many such as Schnohr and Marott (2011) got close to dealing with the fact that extreme sprinting and nothing (as a barbell) outperforms steady exercise, but missed the convexity bias part.

Art De Vany and Jensen’s inequality:
Art De Vany, private correspondence: “Tissue gains are increasing but convex with nutrient intake (the curve is rising, but at a diminishing rate). This has to be the case for the point of origin to be a steady state solution. This implies that weight gain, including fat, is higher at the average intake than it is on a varying intake of the same calories and nutrients. Muscle and fat compete for substrate, so a fatter person will shift nutrient partitioning toward muscle because body fat induces insulin resistance in muscle. Insulin operates in a pulsate release and is far more effective with that pattern than with the chronic elevation induced by six meals a day. On the downside, where fat and muscle are lost, the curve is negatively sloped but declines at a diminishing rate (concave). This means you lose more fat feeding intermittently than continuously. The loss at the average intake (six per day keeps the variation of the average small) is less than the loss at the same intake but one that varies between a small intake and a large one. A more subtle point: you lose more weight when you eat at the average than intermittently, but that is because you lose more muscle in chronic deprivation than intermittent deprivation. Intermittent eating yields a superior body composition.”

Starvation, intermittent fasting, and aging:
For the neuronal resistance and brain aging, Anson, Guo, et al. (2003), Mattson et al. (2005), Martin, Mattson et al. (2006), Halagappa, Guo, et al. (2007), Stranahan and Mattson (2012).

Caloric restriction:
Harrison (1984), Wiendruch (1996), Pischon (2008).

Intense exercise:
Synthesis of the literature on the effect of episodic energy imbalance, in De Vany (2011), who also, as a bonus, examines powerlaw effects.

Missing the point that pills are more speculative:
Stip (2010) spends time on
via positiva
methods to extend life with complicated pharma stories.

Glucose and willpower:
Note the effect of glucose making people sharper and helping willpower from experiments by Baumeister, see Kahneman (2011), might only apply to metabolically unfit persons. See Kurzban (2011) for a look at the statistical tools.

Cluster of ailments from lack of randomness, as presented in prologue:
Yaffe and Blackwell (2004), Razay and Wilcock (1994); Alzheimer and hyperinsulenemia, Luchsinger, Tang, et al. (2004), Janson, Laedtke, et al. (2004).

Starvation and the brain:
Stranahan and Mattson (2012). Long-held belief that the
brain needed glucose, not ketones, and that the brain does not go through autophagy, progressively corrected.

Ramadan and effect of fasting:
Ramadan is not interesting because people fast for only about 12 hours, depending on the season (someone who fasts from dinner to lunch can get 17 hours without food, which is practiced by this author). Further, they gorge themselves at dawn, and load on carbohydrates with, in my experience, the sweets of Tripoli (Lebanon). Nevertheless, some significance. Trabelsi et al. (2012), Akanji et al. (2012).

Benefits of stress:
For the different effects of the two types of stressors, short and chronic, Dhabar (2009); for the benefits of stress on boosting immunity and cancer resistance, Dhabhar et al. (2010), Dhabhar et al. (2012).

Iatrogenics of hygiene and systematic elimination of germs:
Rook (2011), Garner et al. (2006), Mégraud and Lamouliatte (1992) for Helyobacter.

The Paleo crowd, De Vany, Gary Taubes, and friends:
Taubes (2008, 2011), De Vany (2011); evolutionary anthropology, Carrera-Bastos et al. (2011), Kaplan et al. (2000).

Modern philosophical discussions on capitalism:
No interest in such a simple heuristic as skin in the game, even in insightful discourses such as Cuillerai (2009).

Courage in history:
Berns et al. (2010).

Gladiators:
Veyne (1999).

Treadmill:
Lucretius,
Nimirum quia non bene norat quæ esset habendi / Finis, et omnino quoad crescat vera voluptas.

Group and collective:
Haidt (2012).

Adam Smith on capitalism:
“A word he never uttered”: Simon Schama, private communication.

Stiglitz et al. dangerous report:
Joseph E. Stiglitz, Jonathan M. Orszag, and Peter R. Orszag, “Implications of the New Fannie Mae and Freddie Mac Risk-based Capital Standard,”
Fannie Mae Papers,
Volume I, Issue 2, March 2002.

Meyer Lansky:
Attributed to Ralph Salerno, retired NYPD mob investigator, in Ferrante (2011).

Unsavory activities by pharma finding patients rather than treatments:
Stories of direct and indirect corruption, particularly in the psychiatric domain. A professor of psychiatry at Harvard Medical School received $1.6 million from pharma. “Thanks to him, children as young as two years old are now being diagnosed with bipolar disorder …” Marcia Angell,
The New York Review of Books
. Angell used to be the editor of
The New England Journal of Medicine
and distrusts a large number of clinical studies. Further, how money is not spent on speculative research, but on “safe” bets with regular drugs, Light and Lexchin (2012).

Contradicting studies:
Kahneman brought to my attention studies such as Malmendier and Tate (2008, 2009) showing managers investing more than needed in their companies, hence excess skin in the game as a result of overconfidence. Myron Scholes and Robert Merton had investments in LTCM. Indeed—but overall the free option dominates (just measure the aggregate payment of managers relative to gains by shareholders). There are “fools of randomness” and “crooks of randomness”; we often observe a combination. (Credit: Nicolas Tabardel.)

Asymmetries and extractive:
Acemoglu and Robinson (2012) discusses an asymmetry with their notion of extractive economic institutions and environment, in which someone gets rich at the expense of someone else, the opposite of the convex
collaborative framework in which one’s wealth leads to a compounding pie. Role of institutions, North (1990).

Caviar socialism and Burnyeat’s problem:
Riffard (2004), Burnyeat (1984), Wai-Hung (2002).

Collective blindness and diffusion of responsibility:
In the animal domain (ants), Deneubourg, Goss et al. (1983), Deneubourg, Pasteels et al. (1983).

Life and socialization in Rome:
Veyne (2001).

Elephant in the room:
Things that everyone knows but remain undiscussed. Zerubavel (2006).

Mortality of large firms:
Higher than expected, Greenwood and Suddaby (2006), comment Stubbart and Knight (2006). The best test is to take the S&P 100 or S&P 500 and look at its composition through time. The other one of course is in the literature on mergers.

Information cascades:
The mechanism by which the crowd exacerbates fallacies, illusions, and rumors, Sunstein (2009) for a synthesis.

Alan Blinder problem:
Wall Street Journal
article with undisclosed conflict of interest: “Blanket Deposit Insurance Is a Bad Idea,” Oct. 15, 2008, coauthored with R. Glenn Hubbard, dean of Columbia University Business School.

Comparative performance of family businesses:
McConaughy and Fialco (2001), Le Breton–Miller and Miller (2006), Mackie (2001).

Skin in the game:
Taleb and Martin (2012a).