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rgejman

672 karma · joined December 26, 2009

http://ron.gejman.com [ my public key: https://keybase.io/rgejman; my proof: https://keybase.io/rgejman/sigs/jXEYtNnNbzvxR-zVpC8bW7XBAdDKvlfIRh2qhvWA3w8 ]
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rgejman··on Google employee resigns after ‘retaliation’ for protesting Israeli contract
The problem from the perspective of many Jews (including myself) is that these kinds of protests and protestors tend to focus on Israel to the exclusion of any other state. Where is the protest of Google's relationships with dozens of other countries accused of major human rights violations? The double standard when it comes to Israel calls into question the motivation behind the protest and makes many Jews reasonably wonder if it is actually anti-semitic (even when coming from fellow Jews).
rgejman··on The Rise and Fall of Polywater
Another good example of bad science related to water is "water memory" (published in Nature!): the idea that water could hold onto the "shape" of molecules with which it was mixed. Fun times. https://en.wikipedia.org/wiki/Water_memory
rgejman··on Re-Thinking Electronic Mail
Emails from a stamped individual could be "whitelisted" so as to no longer require a stamp to show up in your inbox. For instance, the first time you get an email from Amazon Prime (which they pay $0.001 cent to send), a box shows up saying "add this email to a whitelist so they don't have to spend money emailing you?"
rgejman··on A Vaping Illness That’s ‘Becoming an Epidemic’
I remain cautiously pessimistic because there are two main possibilities: (1) there is one product (or a series of products manufactured/purified in the same way) that causes respiratory failure in many or all users, (2) all vaping products have a low level risk of causing respiratory failure. I don't think there is enough data to make a conclusion yet, but I am worried this will end up being a low-level persistent problem with vaping products—bootleg or not—for the rest of our lives.

Maybe the culprit truly is dirty oil based extraction of THC... but if so, that will remains a problem for as long as there is no regulation of the official market as well as an operating black market.

OTOH we may end up with a situation like we have in the world of muscle builder / hormone supplements where most people are fine but some users get really sick (e.g. deer hormones sold at regular stores causing severe kidney injury), but not enough of them get sick to get the CDC/FDA involved. I've seen those cases in the hospital and the patients are always confused as to how this could happen because they got the supplement from a vitamin store.

With respect to some of the European posters below who have been using vape products for years: I would not be surprised if there were health consequences to those devices that had not been identified in Europe. The US has one of the best disease identifying-apparatuses in the world (the Centers for Disease Control) and a tradition of surveillance and reporting that is unparalleled. If a substance is harmful to health, it's got a better chance of being found here than anywhere else.

rgejman··on Uber Posts $5.2B Loss and Slowest Ever Growth Rate
True, true.
rgejman··on Uber Posts $5.2B Loss and Slowest Ever Growth Rate
Is uber just an elaborate vehicle designed to redistribute wealth from investors to cab drivers and computers engineers?
rgejman··on Pock: Display macOS Dock in Touch Bar
Suggestions: an option to only show open/active applications.
rgejman··on Minnesota court decision means doctors can be sued by patients they don't treat
This situation happens in EDs as well. For example: ED attending thinks admission is warranted but patient does not meet criteria (“please come see the patient because he/she looks worse than labs suggest”). This is why the ED exists and the correct move here should have been for the NP to send the patient to the ED for evaluation instead of relying on the opinion of an MD over the phone. The physician at the hospital should have suggested this as well—but to think that the MD is culpable for malpractice without laying eyes on the patient is lunacy.
rgejman··on Minnesota court decision means doctors can be sued by patients they don't treat
Where does it say that? This NP was practicing independently and the Fairview hospital has an ED. There is no reason that if the NP was concerned she should not have sent the patient to the ED.
rgejman··on Minnesota court decision means doctors can be sued by patients they don't treat
I haven't done a deep dive here... but this makes no sense for multiple reasons.

1. It will have a chilling effect on physicians giving informal ("curbside") consults to colleagues. That leads to worse patient care overall. For instance if your doctor doesn't know what's up with you, he/she may not be able to curbside consult phone a colleague to get a 2nd opinion. This happens all the time in medicine and is one of the advantages of being at a medical center with lots of doctors: you can double check weird cases with your colleagues.

2. Direct admission to the inpatient ward are no longer common because outside physicians don't run hospitals anymore. Hospitals are run by teams who specialize in inpatient medicine -- and they almost always function best if the inpatient admission is preceded by an ED visit because the ED can rapidly get tests, imaging and collateral to figure out what's wrong—and if the problem needs inpatient management or not. Direct admissions, in bypassing this step, often put patients at risk by skipping the rapid information gathering process that the ED employs.

The "admitting privileges" they discuss in this article are a relatively meaningless and outdated practice in medicine today (with certain exceptions, such as obstetricians and some other surgeons).

rgejman··on ‘Bubble Boys’ Cured in Medical Breakthrough Using Gene Therapy
Right--see the paper I linked to above for an example of that. Here's a summary article: https://www.cell.com/molecular-therapy-family/molecular-ther...

If you can't access it then shoot me an email at ron gejman at gmail dot com and I'll send you the pdf.

rgejman··on ‘Bubble Boys’ Cured in Medical Breakthrough Using Gene Therapy
Not with this approach. It's easier to add a gene to one cell lineage (in this case, the blood cell forming hematopoietic lineage) than to remove a gene from every single cell in the body.

But there are other strategies in development to help some patients with autoimmune disease. This is one of my favorite papers in that vein: https://www.ncbi.nlm.nih.gov/pubmed/27365313

rgejman··on ‘Bubble Boys’ Cured in Medical Breakthrough Using Gene Therapy
The actual study is here. It's a remarkable achievement: https://www.nejm.org/doi/full/10.1056/NEJMoa1815408

No CRISPR/Cas9 was used in this study.

We'll have to wait and see if any of the patients develop hematologic malignancies (blood cancers).

I predict we'll see dozens of papers like this in the next few years. Sickle cell and thalessemias are low hanging fruit.

rgejman··on Demand is skyrocketing in China for mice that mimic the diseases of humans
In practice you need to maintain large colonies in order to reliably have enough mice for experiments. Also you need to keep gender in mind because females can be housed together but males cannot and generally experiments are conducted in either one gender or the other.

So, let's say you need 20 female mice for an experiment (e.g. 4 groups of 5). That means that you need to have >40 offspring in order to get enough female offspring. That's at least 7 breeding pairs (assuming you're not harem breeding) and you've got to maintain them for 6-8 weeks until you can use them. That's >$1,000 in breeding costs before you get to the actual experiments.

rgejman··on Demand is skyrocketing in China for mice that mimic the diseases of humans
Many things that are done in biology (and medicine to some extent) are way simpler than they seem because much of it was figured out a long time ago using tools that scientists/doctors had at hand.

We grow cells in what is essentially sugar water + some growth factors that we get from cow serum (b/c America has lots of cows). Google tissue culture 101 videos on youtube to get an idea of how it all works. You can't (and don't want) to inject the animals with all that fluid + protein (it can be liters), so you transfer the cells into tubes and spin them in a centrifuge (~300 x g). Spinning them will bring them to the bottom of the tube and they will form a pellet. The pellet sticks to the bottom as you literally dump the fluid out. Now you can resuspend the cells in a few microliters of a saline solution and inject them into the mice.

For example, cells growing in an incubator usually need to be at a density of 200k-1e6/ml so that they have enough nutrients and waste doesn't build up too quickly. For 5e6 cells, that would be 5-25ml of fluid, which is WAY too much to inject into a mouse, so you have to concentrate the cells into a much smaller volume before you can inject. I will typically inject mice with 100µl of fluid containing 5e6 cells.

In terms of injection, you can google subcutaneous injections in mice to see how it's done. It's the same as if you've ever had a tuberculosis skin test or a minor operation where they injected you with lidocaine locally (or what your dentist does). The cancer cells are injected into the space right under the skin.

rgejman··on Demand is skyrocketing in China for mice that mimic the diseases of humans
The expenses associated with animal husbandry at most research institutes raise the price to ~$1/day per cage of 5 mice.
rgejman··on Demand is skyrocketing in China for mice that mimic the diseases of humans
>Mice are so easy to keep, they could be entitely mechanicly reared, and an experiment involving 1000 mice should be a simple matter of a few clicks on a computer.

I invite you to go visit a laboratory that works with rodent models for a few days and see if you still think this is true. I would love to be proven wrong, but in my experience animal experiments are as non-automatable as human clinical trials. As a simple example, in my PhD I spent months injecting mice with cancer cells, measuring the tumor outgrowth, then harvesting the tumors, grinding them up and sequencing them. You can see the schematics of some of those experiments in one of my manuscripts (https://elifesciences.org/articles/41090 -- free to access). Each one of those experiments relied on dozens of different techniques (from cloning to making viruses to culturing cells to animal husbandry), most of which are not easy to automate because they vary from experiment to experiment. For instance, just to grow the cells for injection into animals, you need to monitor plates of cells growing in a sealed 37º incubator, wash and re-feed them as necessary over a period of days to weeks. Then, on the day of injection, you need to wash and spin them down, resuspend in an injection solution, put them on ice, go down to the mouse house, shave the mice, anesthetize them and then inject them. You don't want too much time to elapse between when you prep the cells and when you inject them or they might die. At every step there are biosafety constraints that limit your movements and how you dispose of garbage which would be challenging to scale up to a totally automated system. Every different cell line/type you inject has different kind of growth requirements and idiosyncrasies in how they like to be handled. I suppose you could program machines to do this for one cell line, but it would be a monumentally difficult task to do it for every cell line and get good results. Then there's the matter of just handling the animals. I would love to see a machine that could do this (and maybe one day there will be) but for the moment you need training in how to carefully and safely grab mice, restrain them, inject them and so on.

The costs of maintaining mice is also much larger than it seems (perhaps compared to mice kept as pets). A major cost is the daily tasks associated with husbandry, like cleaning cages, sick checks, genotyping, etc. At least at my institute it was ~$1.50 per day per cage (up to 5 mice) in support costs, not including the ~$30-50 it costs to raise a wild-type mouse to the point where you could do the experiment (more for some genetically modified mice). An experiment with 500 mice (100 x 5 conditions) would cost you $15-20k, which would massively balloon the cost of research.

Finally, there are major ethical concerns with using more animals than necessary for any experiment. Animal work is carefully regulated by internal and external ethics committees and oversight of all ongoing experiments. The number of animals to be used for any given project must be justified with statistical analysis suggesting that you are using no more than necessary and will indeed be able to show the expected results. If you propose experiments using large numbers of animals you must have a good explanation for why you need such numbers.

Anyway, it's not really that simple or cheap to do animal experiments, especially at large scale.

rgejman··on Texans say voting machines changing straight-ticket choices
This is a forum populated with thousands of smart and talented engineers all discussing the absurdity of US voting systems and suggesting great fixes. There is clearly a problem to be solved here—and it might even be lucrative to solve it. Seems like a reasonable idea for a startup company: making cheap, audit-able polling devices that can be sold to any county in the country and any country in the world. Someone here should take a stab at it.
rgejman··on Birth Rates Dropped Most in U.S. Counties Where Home Prices Grew Most
This data is also consistent with the idea that people leave expensive areas in order to have children in cheaper areas.
rgejman··on Relative's DNA from genealogy websites cracked East Area Rapist case
I meant the access to commercial DNA databases. Looks like it’s been explained above.
rgejman··on Relative's DNA from genealogy websites cracked East Area Rapist case
Does anyone have any more information on this? How do the police get access to DNA from genealogical databases? Do they need a warrant for a specific persons DNA? Do the police check for matches or does the company?
rgejman··on Dear Humanities Profs: We Are the Problem
You can honor expertise while acknowledging bias and still come up with empirically correct conclusions (otherwise I wouldn't be a scientist) that are based on relatively basic shared values. Expertise is an antidote to propaganda when people think critically about the problems at stake. As the author notes, David Foster Wallace was right that cynicism is lethal; but cynicism can also be enabling in those who are free thinkers. The article raises important points about how we got ourselves into this mess. Good reading. As usual it occurs to me that the goals of scientific exploration are as universal as we get because they aim to (a) discover the unknown and (b) to make the world better through discovery. Take that, humanists!
rgejman··on Network of fortified towns indicates Amazon was once heavily populated
Orson Scott Card wrote a decent but weird scifi book on this premise called "Pastwatch: The redemption of Christopher Columbus." It contains a really graphic description of how a time traveling character convinces the Mayans to trust him by pulling spikes out of his penis. Weird but interesting. https://en.wikipedia.org/wiki/Pastwatch:_The_Redemption_of_C...
rgejman··on Cancer ‘vaccine’ eliminates tumors in mice
The difference between (a) an existing, off-patent molecule and a (b) patentable variant of that molecule is somewhat trivial compared to all of the other costs of bringing a drug to market.

But to address your specific question, generics are drugs that come onto the market all of the time without patent protection.

rgejman··on Cancer ‘vaccine’ eliminates tumors in mice
This is just not true. Drug companies will make slight modifications to existing drugs and can get new patents on the new formulations and for new indications. If it works, a drug company can make money off of it even if it's been off-patent for years. See https://en.wikipedia.org/wiki/Lenalidomide vs thalidomide for an example.

For every therapeutic target there are many chemical/biological solutions that can work. If an off-patent compound shows some effect in a pathway, a patentable variant can usually be made.

rgejman··on Modifying Your Own Genes Is Just An Injection Away If You’re Feeling Lucky
There are other reasons why flu vaccines don't work from year to year. For instance, this year there is evidence that vaccines made in eggs acquired mutations that limited the effectiveness of the immune response (https://www.statnews.com/2017/11/07/flu-vaccine-egg-producti...). Viruses made by other means don't seem to have this problem but are a lot more expensive and we'd need to retool the entire flu vaccine industry to solve this.
rgejman··on Modifying Your Own Genes Is Just An Injection Away If You’re Feeling Lucky
No it is not that simple. You need a carrier to help the DNA get into cells efficiently. If you want to modify specific cell types then you need a cell type-specific carrier. Today, editing your DNA is "easy" -- targeting the right cells is "hard."
rgejman··on The Most Expensive Mile of Subway Track
I like reading your comments, thinking to myself, "this is something chimeracoder would write" and then seeing that you did in fact write it.
rgejman··on Confessions of a Digital Nazi Hunter
Why was this article flagged?
rgejman··on Blockchain Could Help Us Reclaim Control of Our Personal Data
On #1: I hear you and I think this is a totally valid approach for a society where we don't have little old ladies and gents who lose the piece of paper on which they've written their key and all their friends are old and they urgently need their secure key so that the doctor can access their health records. Or the kid who comes into the hospital in a coma and you can't get their secure key. Or for the recent immigrant family with no friends and their house burns down with all their secure keys inside. Or for the gay kid who gets kicked out of his house without taking his key and the people that blockchain "trusts" are his parents who just threatened to kill him if he comes home.

The "use case" here is people's lives. People's lives are messy. Blockchain doesn't solve that mess, it pretty much just makes it worse.

We should focus on using blockchain to solve "neater" problems like who owns what and who is contractually obligated to do what, etc. Those problems don't have edge cases that involve a parent who loses their memory or a kid who gets thrown out of his house.

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