Author Archives: curiouscat

George Box 1919 to 2013 – A Great Friend, Scientist and Statistician

I would most likely not exist if it were not for George Box. My father took a course from George while my father was a student at Princeton. George agreed to start the Statistics Department at the University of Wisconsin – Madison, and my father followed him to Madison, to be the first PhD student. Dad graduated, and the next year was a professor there, where he and George remained for the rest of their careers.

George died today, he was born in 1919. He recently completed An Accidental Statistician: The Life and Memories of George E. P. Box which is an excellent book that captures his great ability to tell stories. It is a wonderful read for anyone interested in statistics and management improvement or just great stories of an interesting life.

George Box by Brent Nicastro.

George Box was a fantastic statistician. I am not the person to judge, but from what I have read one of the handful of most important applied statisticians of the last 100 years. His contributions are enormous. Several well know statistical methods are known by his name, including:

George was elected a member of the American Academy of Arts and Sciences in 1974 and a Fellow of the Royal Society in 1979. He also served as president of the American Statistics Association in 1978. George is also an honorary member of ASQ.

George was a very kind, caring and fun person. He was a gifted storyteller and writer. He had the ability to present ideas so they were easy to comprehend and appreciate. While his writing was great, seeing him in person added so much more. Growing up I was able to enjoy his stories often, at our house or his. The last time I was in Madison, my brother and I visited with him and again listened to his marvelous stories about Carl Pearson, Ronald Fisher and so much more. He was one those special people that made you very happy whenever you were near him.

George Box, Stuart Hunter and Bill Hunter (my father) wrote what has become a classic text for experimenters in scientific and business circles, Statistics for Experimenters. I am biased but I think this is acknowledged as one of (if not the) most important books on design of experiments.

George also wrote other classic books: Time series analysis: Forecasting and control (1979, with Gwilym Jenkins) and Bayesian inference in statistical analysis. (1973, with George C. Tiao).

George Box and Bill Hunter co-founded the Center for Quality and Productivity Improvement at the University of Wisconsin-Madison in 1984. The Center develops, advances and communicates quality improvement methods and ideas.

The Box Medal for Outstanding Contributions to Industrial Statistics recognizes development and the application of statistical methods in European business and industry in his honor.

“All models are wrong but some are useful” is likely his most famous quote. More quotes By George Box

A few selected articles and reports by George Box

William G. Hunter: An Innovator and Catalyst for Quality Improvement
The Scientific Context of Quality Improvement
Statistics for Discovery
Statistics as a Catalyst to Learning by Scientific Method
Improving Almost Anything – collection of great articles and reports

Cell Aging and Limits Due to Telomeres

When cells divide the process fails to copy DNA all the way to the end. Telomeres are are the end of DNA strands, as essentially a buffer of material that won’t cause information to be lost when part of the telomere isn’t copied. As DNA is copied, as new cells are created, the length of telomeres at the end is reduced. Once the telomeres are gone the cell will no longer divide.

The 2009 Nobel Prize in Physiology or Medicine went to 3 scientists for discovering how the chromosomes can be copied in a complete way during cell divisions and how they are protected against degradation. The Nobel Laureates have shown that the solution is to be found in the ends of the chromosomes – the telomeres – and in an enzyme that forms them – telomerase.

There is some debate over the benefit of the mechanism of cells not dividing do to lack of telomere. This can prevent cancerous cells from replicating (once they replicate to the extent that the necessary telomere buffer is gone). It is also seen that as telomeres get shorter the cells become more likely to become cancerous.

Cancer also can stimulate the production of telomerase which can stop telomeres from getting shorter as cells divide and thus allow the cancer cells to keep dividing (thus producing more cancer cell and increasing the amount of cancerous cells). Using telomerase to allow health cells to avoid the limits of division is being researched.

Are Telomeres the Key to Aging and Cancer? (University of Utah)

An enzyme named telomerase adds bases to the ends of telomeres. In young cells, telomerase keeps telomeres from wearing down too much. But as cells divide repeatedly, there is not enough telomerase, so the telomeres grow shorter and the cells age.
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Cells normally can divide only about 50 to 70 times, with telomeres getting progressively shorter until the cells become senescent, die or sustain genetic damage that can cause cancer.
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shorter telomeres are associated with shorter lives. Among people older than 60, those with shorter telomeres were three times more likely to die from heart disease and eight times more likely to die from infectious disease.

While telomere shortening has been linked to the aging process, it is not yet known whether shorter telomeres are just a sign of aging – like gray hair – or actually contribute to aging.

Huge Human Population Boom 40,000 to 50,000 Years Ago

Interesting open access paper on looking at the Y-chromosome to explore our ancestry: A calibrated human Y-chromosomal phylogeny based on resequencing. I can’t understand all the details but the basic idea isn’t that complicated. It is interesting to see these details as are the conclusions that can be drawn: that we had a big explosion of human population o 41,000–52,000 years ago.

This population explosion occurred, between the first expansion of modern humans out of Africa 60,000 to 70,000 years ago and the Neolithic expansions of people in several parts of the world starting 10,000 years ago.

“We think this second, previously unknown population boom, may have occurred as humans adapted to their new environment after the first out-of-Africa expansion,” says Dr Qasim Ayub, lead author from the Wellcome Trust Sanger institute. “We think that when humans moved from the horn of Africa to Asia, Australia and eventually Europe, they remained in small groups by the coasts. It took them tens of thousands of years to adapt to the mountainous, forested surroundings on the inner continents. However, once their genetic makeup was suited to these new environments, the population increased extremely rapidly as the groups travelled inland and took advantage of the abundance of space and food.”

The work highlights how it is now possible to obtain new biological insights from existing DNA sequencing data sets, and the value of sharing data. The majority of the DNA information used for this study was obtained from freely-available online data-sets.

This is the first time researchers have used the information from large-scale DNA sequencing to create an accurate family tree of the Y chromosome, from which the inferences about human population history could be made.

Full press release

CDC Again Stresses Urgent Need to Adjust Practices or Pay a Steep Price

Untreatable and hard-to-treat infections from Carbapenem-resistant Enterobacteriaceae (CRE) germs are on the rise among patients in medical facilities. CRE germs have become resistant to all or nearly all the antibiotics we have today. Types of CRE include Klebsiella pneumoniae Carbapenemase (KPC) and New Delhi metallo-beta-lactamase (NDM). By following the United States Center for Disease Control (CDC) guidelines, we can slow the penetration of CRE infections in hospitals and other medical facilities and potentially spread to otherwise healthy people outside of medical facilities.

The CDC has worked with hospitals to successfully apply these measures. The CDC worked with Florida to stop a year-long CRE outbreak in a long-term acute care hospital. With the improved use of CDC recommendations (such as educating staff; dedicating staff, rooms, and equipment to patients with CRE; and improving use of gloves and gowns) the percentage of patients who got CRE at the facility dropped from 44% to 0.

One travesty has been how poorly health care professionals have been about prescribe antibiotics wisely We need to improve and follow CDC antibiotics guidelines (stop the overuse of antibiotics) and use culture results (for patients undergoing treatment) to modify prescriptions, if needed. Antibiotic overuse contributes to the growing problems of Clostridium difficile (c-diff) infection and antibiotic resistance in healthcare facilities. Studies indicate that nearly 50% of antimicrobial use in hospitals is unnecessary or inappropriate (per CDC web site).

Israel decreased CRE infection rates in all 27 of its hospitals by more than 70% in one year with a coordinated prevention program. The USA is at a critical time in which CRE infections could be controlled if addressed in a rapid, coordinated, and consistent effort by doctors, nurses, lab staff, medical facility leadership, health departments/states, policy makers, and the federal government.

As I have been saying for years the damage we are creating due to our actions around the use and abuse of antibiotics is likely to kill tens of thousands, or more people. Because the deaths are delayed and often not dramatic we have continued dangerous practices for years when we know better. It is a shame we are condemning so many to increased risks. The CDC, and others, are doing good work, unfortunately too much bad work is continuing in the face of evidence of how dangerous that is.

Introduction Video on 3D Printing

3D printing is an amazing technology that opens up great opportunities for us to enjoy life. The future is great. It is exciting to see how quickly advances are being made in this area. I think the ability to print replacement parts is a huge benefit. And the creative uses people will put these printers too will be a joy to see.

People are Superorganisms With Microbiomes of Thousands of Species

In a recent article in National Geographic Carl Zimmer has again done a good job of explaining the complex interaction between our bodies and the bacteria and microbes that make us sick, and keep us healthy.

The damage done by our indiscriminate use of antibiotics is not just the long term resistance that we create in bacteria (making the future more dangerous for people) that I have written about numerous times but it also endangers the person taking the anti-biotics in the short term. Sometimes the other damage is a tradeoff that should be accepted. But far too often we ignore the damage taking antibiotics too often does.

When You Swallow A Grenade

While antibiotics can discriminate between us and them, however, they can’t discriminate between them and them–between the bacteria that are making us sick and then ones we carry when we’re healthy. When we take a pill of vancomycin, it’s like swallowing a grenade. It may kill our enemy, but it kills a lot of bystanders, too.
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If you think of the human genome as all the genes it takes to run a human body, the 20,000 protein-coding genes found in our own DNA are not enough. We are a superorganism that deploys as many as 20 million genes.
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Before he started taking antibiotics, the scientists identified 41 species in a stool sample. By day 11, they only found 13. Six weeks after the antibiotics, the man was back up to 38 species. But the species he carried six weeks after the antibiotics did not represent that same kind of diversity he had before he took them. A number of major groups of bacteria were still missing.
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They found that children who took antibiotics were at greater risk of developing inflammatory bowel disease later in life. The more antibiotics they took, the greater the risk. Similar studies have found a potential link to asthma as well.

The human body contains trillions of microorganisms — outnumbering human cells by 10 to 1. Because of their small size, however, microorganisms make up only about 1% to 3% of the body’s mass, but play a vital role in human health.

Where doctors had previously isolated only a few hundred bacterial species from the body, Human Microbiome Project (HMP) researchers now calculate that more than 10,000 microbial species occupy the human ecosystem. Moreover, researchers calculate that they have identified between 81% and 99% of all microorganismal genera in healthy adults.

“Humans don’t have all the enzymes we need to digest our own diet,” said Lita Proctor, Ph.D., NHGRI’s HMP program manager. “Microbes in the gut break down many of the proteins, lipids and carbohydrates in our diet into nutrients that we can then absorb. Moreover, the microbes produce beneficial compounds, like vitamins and anti-inflammatories that our genome cannot produce.” Anti-inflammatories are compounds that regulate some of the immune system’s response to disease, such as swelling.

“Enabling disease-specific studies is the whole point of the Human Microbiome Project,” said Barbara MethÃ©, Ph.D., of the J. Craig Venter Institute, Rockville, MD, and lead co-author of the Nature paper on the framework for current and future human microbiome research. “Now that we understand what the normal human microbiome looks like, we should be able to understand how changes in the microbiome are associated with, or even cause, illnesses.”

Read the full NIH press release on the normal bacterial makeup of the body

Scientists Don’t Look Like They Do in Movies

The Myth of the Scientist: Crystal Dilworth at TEDxYouth@Caltech

Scientists don’t fit the stereotypical mold some people think they do. It doesn’t take much to replace those views. The main point, in my opinion, is to let kids know they can be a scientists even if they are not like the stereotypical examples – though it will take a lot of work.

Continue reading →

Human Gene Origins: 37% Bacterial, 35% Animal, 28% Eukaryotic

The percent of human genes that emerged in various stages of evolution: 37% bacterial, 28% eukaryotic, 16% animal, 13% vertebrate, 6% primate. The history that brought us to where we are is amazing. Eukaryotes include animals, plants, amoebae, flagellates, amoeboflagellates, fungi and plastids (including algae). So eukaryotic genes are those common to us and other non-animal eukaryotes while those classified as animal genes are shared by animals but not non-animal eukaryotes.

We are living in a bacterial world, and it’s impacting us more than previously thought by Lisa Zyga

Bacterial signaling is not only essential for development, it also helps animals maintain homeostasis, keeping us healthy and happy. As research has shown, bacteria in the gut can communicate with the brain through the central nervous system. Studies have found that mice without certain bacteria have defects in brain regions that control anxiety and depression-like behavior. Bacterial signaling also plays an essential role in guarding an animal’s immune system. Disturbing these bacterial signaling pathways can lead to diseases such as diabetes, inflammatory bowel disease, and infections. Studies also suggest that many of the pathogens that cause disease in animals have “hijacked” these bacterial communication channels that originally evolved to maintain a balance between the animal and hundreds of beneficial bacterial species.
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Scientists have also discovered that bacteria in the human gut adapts to changing diets. For example, most Americans have a gut microbiome that is optimized for digesting a high-fat, high-protein diet, while people in rural Amazonas, Venezuela, have gut microbes better suited for breaking down complex carbohydrates. Some people in Japan even have a gut bacterium that can digest seaweed. Researchers think the gut microbiome adapts in two ways: by adding or removing certain bacteria species, and by transferring the desired genes from one bacterium to another through horizontal gene transfer. Both host and bacteria benefit from this kind of symbiotic relationship, which researchers think is much more widespread than previously thought.
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We want badly for the message in ‘Animals in a bacterial world,’ to be a call for the necessary disappearance of the old boundaries between life science departments (e.g., Depts of Zoology, Botany, Microbiology, etc.) in universities, and societies (e.g., the American Society for Microbiology, etc.). We also want the message disseminated in college and university classes from introductory biology to advanced courses in the various topic areas of our paper.”

Very cool stuff. This amazing facts scientists discover provide an amazing view of the world we live in and how interconnected we are to other life forms in ways we don’t normally think of.

How to Walk on Ice

infographic explaining how to walk on ice - walk like a penguin

Infographic by Tablet. Falling on ice leads to many injuries and even 60 deaths a year in the USA (about the number that will die due to tornados). The graphic encourages thinking like a penguin. Penguins walk well on ice (in some ways) and they also fall well.

Seeking to keep your weight well supported (short strides) is wise (and sliding instead of picking up your feet can help). Falling well is also important. It is basic physics, you want to lower your center of gravity if you are start to slip and avoid any excessive force (so sliding is better than trying to stick out your hand and support all your weight). The elderly are especially susceptible to injuries – avoiding taking direct shocks to the wrist, knees or hips is wise). It does seem kind of silly to learn how to fall but it is very helpful in avoiding injuries.

On sidewalks if you are going to fall and there is snow piled up off the sidewalk, falling into the pile of snow may well be softer than falling directly onto the sidewalk.

On ice you have lower friction so strategies that require friction are not useful – quick moves often rely on very sturdy bases (which are based on the friction of our shoe on for example concrete [which normally is good – though business shoes are not very good] and on ice [where it is very poor – sliding and gradual moves are better]).

Open Source Ecology: Using Open Engineering to Create Economic Benefit

Open Source Philosophy. from Open Source Ecology on Vimeo.

I think the video’s message is overly simplistic and unrealistic (great innovations often seem unrealistic so I don’t mind people trying things I don’t think are likely to succeed in the ways they imagine). But I believe in the concepts of using our knowledge to use appropriate technology to make the standard of living better for everyone. Open access to scientific knowledge is important to such efforts and to the economic well being of modern society.

Open Source Ecology provides a modular, DIY (open access), low-cost, high-performance platform that allows for the easy fabrication of the 50 different Industrial Machines that it takes to build a small, sustainable civilization with modern comforts. The are recruiting for an Operations Manager, and an Executive Team (based in Kansas City or New York City in the USA).