Scanning – Tumors and G+

Scanning – Tumors and G+

So I’m at work catching up on scanning some slides of human squamous cell carcinoma tumors, SCC61. Actually they are xeongrafts in mice legs. The hematoxylin and eosin stains (http://goo.gl/Sq9Eq) make it easy to identify cancer (the purple part, the pink part is muscle). While I’m scanning each slide, I was also catching up on G+. I click on a post from Buddhini Samarasinghe that she warns is long but worth the read (http://goo.gl/tiZtc). It’s an interview with Dr. Otis Brawley about his book, “How We Do Harm: A Doctor Breaks Ranks About Being Sick in America”.

He works at Grady hospital in Atlanta, is currently chief medical officer at the American Cancer Society, and graduated from the University of Chicago. Grady sounds like Cook County hospital in Chicago (think ER TV show, now called Stroger), you wouldn’t want to go there but a lot of cops do because they are very experienced in GSW-trauma. Chicago is still the #1 segregated city (http://goo.gl/Vyio8). …the abstract, scholarly term “health disparities” acquires a very real smell of a rotting breast.

Here is the problem: Poor Americans consume too little healthcare, especially preventive healthcare. Other Americans-often rich Americans-consume too much healthcare, often unwisely, and sometimes to their detriment. The American healthcare system combines famine with gluttony.

I don’t want to quote the whole article but I ♥ the Wayne Gretzky quote, “You miss every shot you don’t take”.

There’s so much of the article that resonated with me. I do cancer research. I work in an urban hospital where I see firsthand, the disparities he speaks of. I know breast cancer survivors and our group does breast cancer research. Previous post on breast MRI. http://goo.gl/VSrU4 He’s taken heat about PSA testing but it is something we talk about at work quite often and agree with him.

Anyway, enough babbling. Read the post from Buddhini Samarasinghe

#ScienceEveryday #CancerResearch

Evolutionary forces – Working Together

Evolutionary forces – Working Together

By examining the skulls of primates and connecting the structure and function of bones Dr. Ross et al hopes to better understand the evolutionary forces that drive variations in the skulls of primates. Dr. Ross brought primate skulls on loan from the Field Museum of Natural History to the lab and I imaged them with our microCT (x-ray computed tomography) which I’ve discussed in previous #ScienceSunday posts. The theme for today’s ScienceSunday is collaborative research. So I collaborated with Erin Kane to present my collaboration with Dr. Ross. Just as in real life, working together, we can get more done and complement each other. Thanks to Erin for the beautiful write up below.

Primate Eyes

One of the defining features of all primates is our binocular vision. As primates’ ancestors took to the trees, being able to accurately judge distances gave individuals a selective advantage – you survived jumps and were able to have more offspring than individuals without depth perception who broke bones or fell out of trees. The development of binocular vision may also have helped early primates hunt insects better.

The evolution of binocular vision involved moving eyes from the side of the head (like a horse) to the front of our face, where they are today. When primates’ eyes moved to the front of their faces, this changed the distribution of forces exerted on the skull, especially when chewing. Over time, primate ancestors developed a bony ridge, called a post-orbital bar, behind their eye that kept the forces of chewing from deforming the skull and squishing the eyeball.

Tupaia is a tree shrew, one of primates’ closest relatives. Their eyes are on the sides of their faces, so their post-orbital bar isn’t complete. Cheirogaleus, the fat-tailed dwarf lemur, is a prosimian, a relatively primitive modern primate (http://goo.gl/ti65p). It’s skull is very similarly shaped to Tupaia, but it has a complete post-orbital bar, and it’s eyes are closer to the front of its face. Tuapaia is a lot like the proto-primates, organisms called plesiadapids who are likely primates’ ancestors. Cheirogaleus is a pretty good analogy for some of the early primates – nocturnal, probably eating insects, and living solitarily.

About the same time monkeys evolved, primates’ eyes shifted to the front of their faces. In response to the shift in forces from the eyes moving further to the front of their faces, monkeys and apes developed a solid plate of bone at the back of their eyes. Saguinus and Aotus are both South American monkeys with that solid plate of bone at the back of their eyes. Sagiunus is a diurnal monkey, active during the day. Its eyes are much smaller than Aotus, the only nocturnal monkey. Nocturnal primates have really large eyes (compare Aotus and Cheirogaleus) in order to get as much light as possible into their eyes.

Enjoy your collaborations, Memorial Day in the US, and The Monkees.

The Monkees – “Pleasant Valley Sunday” – ORIGINAL VIDEO – HQ

Instead of Monkee (primate) eyes, maybe you’ll enjoy Hall and Oates – Private Eyes

Check out the Visage Imaging page for more projects that use Amira.

#ScienceSunday curated by Allison Sekuler and Robby Bowles with Wonder Woman Rajini Rao

Promising new cancer drug screening method

Promising new cancer drug screening method

Dr. M. Bhatia et al at McMaster University in Hamilton, Ontario, Canada (where ScienceSunday curator Allison Sekuler is) developed a new cancer drug screening method using pluripotent stem cells. They found that thioridazine, an anti-psychotic drug, is effective against cancer stem cells without harming normal cells. The screening method specifically looks for drugs that cause cancer stem cells to differentiate.

The news brief is here: http://news.sciencemag.org/sciencenow/2012/05/psychiatric-drug-may-kill-cancer.html?rss=1

and full article here:http://www.sciencedirect.com/science/article/pii/S0092867412005715

#ScienceEveryday #CancerResearch

We don’t live or work in a vacuum

We don’t live or work in a vacuum

Interdisciplinary work and collaborations are the norm for my area of research. So it only makes sense to collaborate with my science friends on G+. Thanks Rajini Rao for giving me the chance to collaborate on a ScienceSunday post. I’m looking forward to everyone’s collaborative posts next Sunday. Unless you have a thick skull (hint) don’t miss my collaborative post with Erin Kane next #ScienceSunday

Originally shared by Rajini Rao

Double your Science Sunday Pleasure: As a theme for next week’s ScienceSunday , Chad Haney proposes Google+ Collaborations. Combine your expertise to create synergy and more awesome #sciencesunday posts. As an example, this beautiful sectioning of a flower, set to the haunting lilts of a waltz, has the hallmark of a post from Rajini Rao . Chad Haney provides expert insight on the imaging. So, what are you waiting for science enthusiasts?

The Beauty Within: Beauty, as they say, lies in the eye of the beholder. Arabidopsis is an insignificant flowering plant of the mustard family (Brassicaceae) that holds special beauty to plant geneticists and molecular biologists. It has only 5 chromosomes, completely sequenced, and a short life span of 6 weeks from germination to seed maturation. A large collection of mutant lines are freely available as a scientific resource, and genes can be readily introduced by infecting with Agrobacterium tumifaciens. A model organism worthy of modeling in this imaging video.

Deconstructing a Flower: 248 sections of an Arabidopsis flower that was paraffin-embedded and sectioned at 20 microns. Sections were stained with Safranin and Fast Green and photographed with a consumer-grade camera mounted on a Nikon Eclipse 50i at 20X.

Chemical clearing vs. digital clearing. The method for plants requires a controlled substance and many samples are too thick for it to work. So they used Adobe After Effects to digitally remove the background making it easier to visualize the sample. They imported JPEGs of each histological slide into AE to create a 3D “stack”. It took 1 hour to align 60 slides after they gained some practice. Images that were lost due to processing issues were excluded. Because they did not use software designed for this, I doubt they were able to get the spacing correct, i.e., have blank slices. There are tons of segmentation algorithms in medial imaging that could have been used. Unfortunately, it would like require some code writing or very expensive medical imaging software. So hats off to them for a cost effective, brute force method. However, as we posted a while ago, the Visible Human Project was funded to develop software that can be used for this project (http://goo.gl/cv2xU).

Video: GRAND PRIZE WINNER in the 3rd ChloroFilms Contest: http://www.ChloroFilms.org

There is a 3D version! Arabidopsis Flower in True 3D

#sciencesunday ScienceSunday Robby Bowles Allison Sekuler

http://www.youtube.com/watch?v=zlw-50RHoec

Knowing R0 number or knowing R. Rao

Knowing R0 number or knowing R. Rao

In 1976 Richard Dawkins coined the term “meme” as a combination of memory and gene.

E. Moro and JL Iribarren of IBM used models of infection to examine how digital information (email) spreads. This was in 2009 before all of the social media exploded. Nevertheless, one important outcome is that people vary in their “infectiousness”. Sometimes it’s not content it’s who gets “infected”.

Phys Rev Lett. 2009 Jul 17;103(3):038702. Epub 2009 Jul 14.

Impact of human activity patterns on the dynamics of information diffusion.

Iribarren JL, Moro E.

http://goo.gl/fWg2D

Summary in NewScientist http://goo.gl/MOxK7

Interesting Interview between Susan Blackmore and Wired.com http://goo.gl/vVGAW

Blackmore gave a TED talk on memes (2008).

http://www.ted.com/talks/susan_blackmore_on_memes_and_temes.html

From the Wired interview:

Wired: What about things that get rooted in popular culture despite an aversion to them and a desire for them to go away? For example, how is it possible that the Paris Hilton meme hasn’t reached the end of its shelf life yet?

Blackmore: Presumably because it presses enough human buttons — you know, sex, greed, celebrity. Some memes will succeed because they make you talk about them even though you think they’re bad. For example, a horrible story about murder or torture upsets you. And one of the ways you try to cope with the upset is to tell somebody else, to share the burden, and that way it spreads and upsets more people, even though you wish it wouldn’t.

Which reminds me of the #ReptileThursday meme where some guy used the hashtag to complain about #ReptileThursday . Since #ReptileThursday was trending, his comment showed up there and people piled on more, in response to his comment.

BTW, if you have me circled then you know I ♥ memes. What’s your R0 number (basic reproduction number in epidemiology studies, memes in this case)?

#ScienceSunday ScienceSunday curated by Allison Sekuler Robby Bowles and Rajini Rao

Dunning–Kruger effect

Dunning–Kruger effect

From the Wiki: The Dunning–Kruger effect is a cognitive bias in which unskilled individuals suffer from illusory superiority, mistakenly rating their ability much higher than average. This bias is attributed to a metacognitive inability of the unskilled to recognize their mistakes.

http://en.wikipedia.org/wiki/Dunning%E2%80%93Kruger_effect

It came up in Filippo Salustri post here: http://goo.gl/Pw2C6 and then in the share below by praveen kulkarni

The video explains it well and it’s true we come across it (unfortunately) quite often in online discussions. The video touches on another issue, which is confusing opinion and fact. The Dunning-Kruger effect seems to explain how one could confuse opinion and fact in an argument. It might even partially explain the anti-science movement.

Nevertheless, it’s an interesting video that was very timely. Thanks for the share praveen kulkarni

Maybe people that follow ScienceSunday would care to start a discussion about the Dunning-Kruger effect.

Originally shared by Praveen Kulkarni

The skills involved in being competent in some area are often the same skills needed to evaluate that competence.

Example : say, in a debate, the skills needed to put forward a logical argument are the same as those to recognize a logical argument

So the skills for doing and assessing go together.

– Diane Kruger effect

http://www.youtube.com/watch?v=XyOHJa5Vj5Y

Don’t add fuel to the anti-science fire

Don’t add fuel to the anti-science fire

Others and I have talked about the lack of publishing negative results. That’s a problem and I agree that bias is a problem. However, Sarewitz’s example of mouse models as an example of bias is horrible and to me disingenuous. There is no question that mouse models aren’t directly related to humans. There are a ton of reasons to use mouse models first. If you look at the FDA requirements for drugs you have to use at least one large species before moving on to human trials. No one expects to get direct data from mice that you can translate to the clinic. However, there are ethical, technical, and economic reasons to do the majority of the basic research using mouse models.

In the commentary by Sarewitz, he mentions the Begley “article” (see below) as evidence that “ironically” industry gets it right. Wrong, here’s my personal example where industry got it wrong and people died.

http://goo.gl/5u6Ov

Here’s my commentary on the Begley commentary.

http://goo.gl/KRlhf

I’m sick of these commentaries that fan the fire of science is bad. I wish there was a “-1” button.

via Misha Belle

Originally shared by mary Zeman

this is a fantastic essay about bias, and the problems we are seeing now in cause-effect/ correlation-causation type assertions in the literature. worth a read.

“Alarming cracks are starting to penetrate deep into the scientific edifice. They threaten the status of science and its value to society. And they cannot be blamed on the usual suspects — inadequate funding, misconduct, political interference, an illiterate public. Their cause is bias, and the threat they pose goes to the heart of research.

Bias is an inescapable element of research, especially in fields such as biomedicine that strive to isolate cause–effect relations in complex systems in which relevant variables and phenomena can never be fully identified or characterized. Yet if biases were random, then multiple studies ought to converge on truth. Evidence is mounting that biases are not random. A Comment in Nature in March reported that researchers at Amgen were able to confirm the results of only six of 53 ‘landmark studies’ in preclinical cancer research (C. G. Begley & L. M. Ellis Nature 483, 531–533; 2012). For more than a decade, and with increasing frequency, scientists and journalists have pointed out similar problems.”

http://www.nature.com/news/beware-the-creeping-cracks-of-bias-1.10600

Industry vs. academic/gov research

Industry vs. academic/gov research

TL;DR there are no more Bell labs. Academic and government agency research is vital for the advancement of science and technology.

This is a partial dialog with Rajini Rao about my personal experience with industry lead or influenced research vs. academic or government research. (Too lazy to write a fresh post). I left the blood substitute field and learned medical imaging because of the state of research for blood substitutes. Blood substitute is a convenient name, just like artificial blood; it’s not really meant to replace whole blood. The research is really about Hemoglobin Based Oxygen Carriers or HBOC. People tried perfluorocarbons but it’s not allosteric like Hb. So you need a lot of oxygen which can be a fire hazard and it causes other issues. Some of the surfactants cause allergies in some people. So the field’s focus is on Hb. Free Hb falls apart and clogs up the kidneys. So Baxter Healthcare and others tried to cross link Hb to keep it as a tetramer. It turns out, that’s not enough. So people, like me, tried polymerizing Hb. I left the field before finding out if any of the large molecular weight formulations had other problems. I suspect there are still other issues since nothing is on the market yet. Oh, and NIH and DoD basically stopped funding research in this area.

Baxter Healthcare’s Hemassist failed clinical trial. There were several preclinical studies showing that it didn’t really work using the same compound made by the Army. Baxter claimed it was not the same formulation and proceeded with the clinical trial. Several patients died, prompting Baxter to halt the trial prematurely. I suspect that some of the people doing research with Baxter did not publish the negative results prominently enough.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728196/

From this review: “The study also criticizes the lack of timely data put forth by the companies and the lack of published studies. Both Hemopure and Polyheme published studies only several years after the completion of their trials. Additionally, unpublished studies render a thorough IRB review of trials difficult. Natanson et al. argue for the timely and complete disclosure of data to the scientific community to avoid exposing the public to unnecessary risks.”

From Rajini Rao: Oh I see, thanks. Interesting problem. It’s more about protein engineering of Hb to make it both efficient and stable as well as nontoxic. The little red cell does a good job of that.

The RBC could be fodder for the intelligent design folks. Well except for sickle cell. I’ve said in other threads when conservatives say that private industry can do better than government funded research such as NIH, NSF, or NASA, just look at Baxter, they are a huge company that dumped millions into to blood substitute research. What happened? People died in clinical trials and we still don’t have a product. The other startups have either failed or have stalled. The difference is private industry has to answer to shareholders and they don’t have to know why or how something works. They just have to find something that works. Academic research aims to find out why and how something works so that we can do it better in the future. So yea, without government funding, we haven’t been able to do better than RBCs.

A less personal example is in today’s Chicago Tribune.

http://goo.gl/tmMO2

TL;DR The flame retardant industry misused and misquoted research to say that flame retardants have a 15-fold increase in “escape time”. The author of one of the papers says “The fire just laughs at it”.

#scienceeveryday