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Telomeres Tell A Lot


Conventional wisdom, indeed wisdom of any form, indicates that physical activity, a.k.a. regular exercise, is good for you.  In particular, intuition would imply that the risk factors for age-related diseases such as diabetes, cancer, hypertension, obesity and osteoporosis would be reduced if people were engaged in physical activity.  To make a direct connection between ageing and physical activity, consider a paper in the Archives of Internal Medicine (Vol.168, No. 2, January 28, 2008), “The Association Between Physical Activity in Leisure Time and Leukocyte Telomere Length” by Cherkas, et al.


“Telomeres consist of tandemly repeated DNA sequences that play an important role in the structure and function of chromosomes.”  Leukocyte telomere length (LTL) is a proxy variable for one’s biological age as opposed to one’s chronological age.  That is, the longer one’s telomeres, the younger one actually is.  Conversely, the shorter the telomeres, the more aged.
==Forsooth==


This study measured the telomeres of 2401 twins who were put into four mutually exclusive categories of physical activity: “Inactive,” “Light,” “Moderate,” and “Heavy” corresponding to “16 minutes, 36 minutes, 102 minutes and 199 minutes” physical activity per week, respectively.  The result after adjusting for “Age, sex, and extraction year” was that the “LTL of the most active subjects (group 4) was an average 200 (SE, 79) nt [nucleotides] longer than that of the inactive subjects (group 1)” producing a p-value of .006.  “This difference suggests that inactive subjects had telomeres the same length as sedentary individuals up to 10 years younger, on average.”   When more complete information was available concerning BMI (biomass index), smoking and SES (socioeconomic status) this reduced the number of subjects to 1531 from the 2401; the LTL difference increased to 213 nt and the p-value increased to .02.  Below are a summary table and Figure 1.
==Quotations==
“We know that people tend to overestimate the frequency of well-publicized, spectacular
events compared with more commonplace ones; this is a well-understood phenomenon in
the literature of risk assessment and leads to the truism that when statistics plays folklore,
folklore always wins in a rout.”
<div align=right>-- Donald Kennedy (former president of Stanford University), ''Academic Duty'', Harvard University Press, 1997, p.17</div>


[[Image:wallis1.png|500px|center]]
----


"Using scientific language and measurement doesn’t prevent a researcher from conducting flawed experiments and drawing wrong conclusions — especially when they confirm preconceptions."
<div align=right>-- Blaise Agüera y Arcas, Margaret Mitchell and Alexander Todoorov, quoted in: The racist history behind facial recognition, ''New York Times'', 10 July 2019</div>
==In progress==
[https://www.nytimes.com/2018/11/07/magazine/placebo-effect-medicine.html What if the Placebo Effect Isn’t a Trick?]<br>
by Gary Greenberg, ''New York Times Magazine'', 7 November 2018
[https://www.nytimes.com/2019/07/17/opinion/pretrial-ai.html The Problems With Risk Assessment Tools]<br>
by Chelsea Barabas, Karthik Dinakar and Colin Doyle, ''New York Times'', 17 July 2019
==Hurricane Maria deaths==
Laura Kapitula sent the following to the Isolated Statisticians e-mail list:
:[Why counting casualties after a hurricane is so hard]<br>
:by Jo Craven McGinty, Wall Street Journal, 7 September 2018
The article is subtitled: Indirect deaths—such as those caused by gaps in medication—can occur months after a storm, complicating tallies
   
   
Laura noted that
:[https://www.washingtonpost.com/news/fact-checker/wp/2018/06/02/did-4645-people-die-in-hurricane-maria-nope/?utm_term=.0a5e6e48bf11 Did 4,645 people die in Hurricane Maria? Nope.]<br>
:by Glenn Kessler, ''Washington Post'', 1 June 2018
The source of the 4645 figure is a [https://www.nejm.org/doi/full/10.1056/NEJMsa1803972 NEJM article].  Point estimate, the 95% confidence interval ran from 793 to 8498.
President Trump has asserted that the actual number is
[https://twitter.com/realDonaldTrump/status/1040217897703026689 6 to 18].
The ''Post'' article notes that Puerto Rican official had asked researchers at George Washington University to do an estimate of the death toll.  That work is not complete.
[https://prstudy.publichealth.gwu.edu/ George Washington University study]
:[https://fivethirtyeight.com/features/we-still-dont-know-how-many-people-died-because-of-katrina/?ex_cid=538twitter We sttill don’t know how many people died because of Katrina]<br>
:by Carl Bialik, FiveThirtyEight, 26 August 2015
----
[https://www.nytimes.com/2018/09/11/climate/hurricane-evacuation-path-forecasts.html These 3 Hurricane Misconceptions Can Be Dangerous. Scientists Want to Clear Them Up.]<br>
[https://journals.ametsoc.org/doi/abs/10.1175/BAMS-88-5-651 Misinterpretations of the “Cone of Uncertainty” in Florida during the 2004 Hurricane Season]<br>
[https://www.nhc.noaa.gov/aboutcone.shtml Definition of the NHC Track Forecast Cone]
----
[https://www.popsci.com/moderate-drinking-benefits-risks Remember when a glass of wine a day was good for you? Here's why that changed.]
''Popular Science'', 10 September 2018
----
[https://www.economist.com/united-states/2018/08/30/googling-the-news Googling the news]<br>
''Economist'', 1 September 2018
[https://www.cnbc.com/2018/09/17/google-tests-changes-to-its-search-algorithm-how-search-works.html We sat in on an internal Google meeting where they talked about changing the search algorithm — here's what we learned]
----
[http://www.wyso.org/post/stats-stories-reading-writing-and-risk-literacy Reading , Writing and Risk Literacy]
[http://www.riskliteracy.org/]
-----
[https://twitter.com/i/moments/1025000711539572737?cn=ZmxleGlibGVfcmVjc18y&refsrc=email Today is the deadliest day of the year for car wrecks in the U.S.]
==Some math doodles==
<math>P \left({A_1 \cup A_2}\right) = P\left({A_1}\right) + P\left({A_2}\right) -P \left({A_1 \cap A_2}\right)</math>
<math>P(E)  = {n \choose k} p^k (1-p)^{ n-k}</math>
<math>\hat{p}(H|H)</math>


Discussion
<math>\hat{p}(H|HH)</math>


1. The article states, “The results of this study can be extrapolated to other white individuals (men and women) of North European origin.”  Find a biologist or a helpful librarian to determine whether it is suspected that non-whites have different telomere lengths and/or have a different distribution.  If so, what does this imply about telomere length and ageing?
==Accidental insights==
2. There were about nine times as many women in the study as men.  Why might this be a concern?
3. Something important is missing in Figure 1 and its absence serves to magnify the average difference.  What is it?
4. The subjects in the study were twins and therefore, attracted extra lay media attention.  Six of the ten authors are affiliated with Kings College, London.  From the Kings College website, “Comparing the telomere lengths of twins who were raised together but take different amounts of exercise, reduces the effect of genetic and environmental variation and so provides a more powerful test of the hypothesis.” Obtain the article and reference #21 to determine why twins as subjects as opposed to non-twins are sort of beside the point. 
5. There was a “discordant twin-pair analysis” performed “as a further confirmation of the larger analysis.”  A paired 2-tailed t test for 67 twin pairs, separated by at least a two category difference is displayed in Figure 2.  What defect does it share with Figure 1?  Why is it even more misleading given that a paired t test is being done? 


My collective understanding of Power Laws would fit beneath the shallow end of the long tail. Curiosity, however, easily fills the fat end.  I long have been intrigued by the concept and the surprisingly common appearance of power laws in varied natural, social and organizational dynamics.  But, am I just seeing a statistical novelty or is there meaning and utility in Power Law relationships? Here’s a case in point.


While carrying a pair of 10 lb. hand weights one, by chance, slipped from my grasp and fell onto a piece of ceramic tile I had left on the carpeted floor. The fractured tile was inconsequential, meant for the trash.
<center>[[File:BrokenTile.jpg | 400px]]</center>
As I stared, slightly annoyed, at the mess, a favorite maxim of the Greek philosopher, Epictetus, came to mind: “On the occasion of every accident that befalls you, turn to yourself and ask what power you have to put it to use.”  Could this array of large and small polygons form a Power Law? With curiosity piqued, I collected all the fragments and measured the area of each piece.


<center>
{| class="wikitable"
|-
! Piece !! Sq. Inches !! % of Total
|-
| 1 || 43.25 || 31.9%
|-
| 2 || 35.25 ||26.0%
|-
|  3 || 23.25 || 17.2%
|-
| 4 || 14.10 || 10.4%
|-
| 5 || 7.10 || 5.2%
|-
| 6 || 4.70 || 3.5%
|-
| 7 || 3.60 || 2.7%
|-
| 8 || 3.03 || 2.2%
|-
| 9 || 0.66 || 0.5%
|-
| 10 || 0.61 || 0.5%
|}
</center>
<center>[[File:Montante_plot1.png | 500px]]</center>
The data and plot look like a Power Law distribution. The first plot is an exponential fit of percent total area. The second plot is same data on a log normal format. Clue: Ok, data fits a straight line.  I found myself again in the shallow end of the knowledge curve. Does the data reflect a Power Law or something else, and if it does what does it reflect?  What insights can I gain from this accident? Favorite maxims of Epictetus and Pasteur echoed in my head:
“On the occasion of every accident that befalls you, remember to turn to yourself and inquire what power you have to turn it to use” and “Chance favors only the prepared mind.”


<center>[[File:Montante_plot2.png | 500px]]</center>
   
   
6. The article states, “A limitation of this type of study is that physical activity level was self-reported.”  Why might this be a limitation?
My “prepared” mind searched for answers, leading me down varied learning paths. Tapping the power of networks, I dropped a note to Chance News editor Bill Peterson. His quick web search surfaced a story from ''Nature News'' on research by Hans Herrmann, et. al. [http://www.nature.com/news/2004/040227/full/news040223-11.html Shattered eggs reveal secrets of explosions].  As described there, researchers have found power-law relationships for the fragments produced by shattering a pane of glass or breaking a solid object, such as a stone. Seems there is a science underpinning how things break and explode; potentially useful in Forensic reconstructions.
7. Assume there is a positive association between LTL and physical activity. Give an alternative explanation to physical activity causing greater telomere length. Give another alternative explanation.
Bill also provided a link to [http://cran.r-project.org/web/packages/poweRlaw/vignettes/poweRlaw.pdf a vignette from CRAN] describing a maximum likelihood procedure for fitting a Power Law relationship. I am now learning my way through that.
 
Submitted by William Montante


Submitted by Paul Alper
----

Latest revision as of 20:58, 17 July 2019


Forsooth

Quotations

“We know that people tend to overestimate the frequency of well-publicized, spectacular events compared with more commonplace ones; this is a well-understood phenomenon in the literature of risk assessment and leads to the truism that when statistics plays folklore, folklore always wins in a rout.”

-- Donald Kennedy (former president of Stanford University), Academic Duty, Harvard University Press, 1997, p.17

"Using scientific language and measurement doesn’t prevent a researcher from conducting flawed experiments and drawing wrong conclusions — especially when they confirm preconceptions."

-- Blaise Agüera y Arcas, Margaret Mitchell and Alexander Todoorov, quoted in: The racist history behind facial recognition, New York Times, 10 July 2019

In progress

What if the Placebo Effect Isn’t a Trick?
by Gary Greenberg, New York Times Magazine, 7 November 2018

The Problems With Risk Assessment Tools
by Chelsea Barabas, Karthik Dinakar and Colin Doyle, New York Times, 17 July 2019

Hurricane Maria deaths

Laura Kapitula sent the following to the Isolated Statisticians e-mail list:

[Why counting casualties after a hurricane is so hard]
by Jo Craven McGinty, Wall Street Journal, 7 September 2018

The article is subtitled: Indirect deaths—such as those caused by gaps in medication—can occur months after a storm, complicating tallies

Laura noted that

Did 4,645 people die in Hurricane Maria? Nope.
by Glenn Kessler, Washington Post, 1 June 2018

The source of the 4645 figure is a NEJM article. Point estimate, the 95% confidence interval ran from 793 to 8498.

President Trump has asserted that the actual number is 6 to 18. The Post article notes that Puerto Rican official had asked researchers at George Washington University to do an estimate of the death toll. That work is not complete. George Washington University study

We sttill don’t know how many people died because of Katrina
by Carl Bialik, FiveThirtyEight, 26 August 2015

These 3 Hurricane Misconceptions Can Be Dangerous. Scientists Want to Clear Them Up.
Misinterpretations of the “Cone of Uncertainty” in Florida during the 2004 Hurricane Season
Definition of the NHC Track Forecast Cone


Remember when a glass of wine a day was good for you? Here's why that changed. Popular Science, 10 September 2018


Googling the news
Economist, 1 September 2018

We sat in on an internal Google meeting where they talked about changing the search algorithm — here's what we learned


Reading , Writing and Risk Literacy

[1]


Today is the deadliest day of the year for car wrecks in the U.S.

Some math doodles

<math>P \left({A_1 \cup A_2}\right) = P\left({A_1}\right) + P\left({A_2}\right) -P \left({A_1 \cap A_2}\right)</math>

<math>P(E) = {n \choose k} p^k (1-p)^{ n-k}</math>

<math>\hat{p}(H|H)</math>

<math>\hat{p}(H|HH)</math>

Accidental insights

My collective understanding of Power Laws would fit beneath the shallow end of the long tail. Curiosity, however, easily fills the fat end. I long have been intrigued by the concept and the surprisingly common appearance of power laws in varied natural, social and organizational dynamics. But, am I just seeing a statistical novelty or is there meaning and utility in Power Law relationships? Here’s a case in point.

While carrying a pair of 10 lb. hand weights one, by chance, slipped from my grasp and fell onto a piece of ceramic tile I had left on the carpeted floor. The fractured tile was inconsequential, meant for the trash.

BrokenTile.jpg

As I stared, slightly annoyed, at the mess, a favorite maxim of the Greek philosopher, Epictetus, came to mind: “On the occasion of every accident that befalls you, turn to yourself and ask what power you have to put it to use.” Could this array of large and small polygons form a Power Law? With curiosity piqued, I collected all the fragments and measured the area of each piece.

Piece Sq. Inches % of Total
1 43.25 31.9%
2 35.25 26.0%
3 23.25 17.2%
4 14.10 10.4%
5 7.10 5.2%
6 4.70 3.5%
7 3.60 2.7%
8 3.03 2.2%
9 0.66 0.5%
10 0.61 0.5%
Montante plot1.png

The data and plot look like a Power Law distribution. The first plot is an exponential fit of percent total area. The second plot is same data on a log normal format. Clue: Ok, data fits a straight line. I found myself again in the shallow end of the knowledge curve. Does the data reflect a Power Law or something else, and if it does what does it reflect? What insights can I gain from this accident? Favorite maxims of Epictetus and Pasteur echoed in my head: “On the occasion of every accident that befalls you, remember to turn to yourself and inquire what power you have to turn it to use” and “Chance favors only the prepared mind.”

Montante plot2.png

My “prepared” mind searched for answers, leading me down varied learning paths. Tapping the power of networks, I dropped a note to Chance News editor Bill Peterson. His quick web search surfaced a story from Nature News on research by Hans Herrmann, et. al. Shattered eggs reveal secrets of explosions. As described there, researchers have found power-law relationships for the fragments produced by shattering a pane of glass or breaking a solid object, such as a stone. Seems there is a science underpinning how things break and explode; potentially useful in Forensic reconstructions. Bill also provided a link to a vignette from CRAN describing a maximum likelihood procedure for fitting a Power Law relationship. I am now learning my way through that.

Submitted by William Montante