If Chocolate Factory is OK for Google and Big Blue is OK for IMB, then
The WinDos Empire
could be OK for Microsoft.
52 posts • joined 30 Aug 2012
There are easily recognisable elements from known antimicrobial principles. I can see three, but mechanistically completely different one. Sulfa, quinoline - and guanidino antiseptics.
The with authors did on mechanism looks sound.
The molecules seem to be stuffed with potentially reactive points, so the road towards clinical acceptance may be a thorny one. Treating a patient may become a race between killing bacteria and harming the patient. If it cures the patient with a single or very few doses, it may become a success. If long treatments are required, I am less optimistic.
Software to analyse the potential for interaction between a drug candidate and selected receptors or enzymes have been in use for a long time - both for finding substances that may have a desired effect, and for weeding out substances with properties that will lead to failure in clinical trials or clinical use. Newer AI systems will have to deliver additional value beyond the expert knowledge of those already in the field. A general tool written by generalists would seem to have a slim chance of being of general use across all those specialist sub-fields within drug discovery - each one requiring biological and technical knowledge way beyond textbooks or published articles.
The market has spoken: The tool wasn't relevant.
The article states that both the psychoactive substances are synthesised as the respective carboxylic acid precursors. They need roasting to become the active stuff (with carbon dioxide leaving), so bread is a relevant vehicle for the oral enjoyment. IIRC the temperature for decomposing the precursors is somewhere around 130 degrees Celcius. Activating the substances in beer requires a very strong autoclave, and you mustn't filter away the yeast.
Anyway, the yields are low. It's probably cheaper and quicker to use imported products from third-world agriculture - if the channels remain open. Commercially I don't think it has much of a chance - except in the UK after the no-deal Brexit.
Response to the drugs in question may be influenced by lots (really) of genetic and nongenetic variables in both the host and the tumour. One part is pharmacokinetics in the host - the overall fate of the drug substance after administration. Another is pharmacokinetics in the tumour - diffusion into areas and cells and organelles where the action takes place. A third is mapping of the pharmacodynamic susceptibility of each malignant clone in the tumour, and the variation of activity-related susceptibility in each cell. And how successful was the surgery?
Details about the behaviour of old anticancer drugs will have to be mainly guesswork with very poor predictive value for an individual patient. Most of the microdetails needed are unavailable to the doctor ahd his/her computer program. And who knows what is relevant, and the weight of each variable?
I would not invest in this project or the people behind it.
With ancient generic drugs the prices may fall so low that maintenance of market presence becomes unprofitable. So some price adjustments are justifiable.
Pyrimethamine has been available from 1953 (https://en.wikipedia.org/wiki/Pyrimethamine). How could that qualify for a patent in the USA? I would think there are more persons than Martin Shkreli who should be investigated or shamed.
"Freedom died a long time ago."
My keyboard entries on the Web are registered. My surfing preferences and emails too. My telephone is tapped and taped. My travels on public transportation are videotaped and registered on my name, and all passages through the road toll registering points are registered and taped.
But I can read whatever I like, love any person I like, travel wherever I like - it's just a question of economic means and keeping up good relations to family, neighbours, colleagues and friends. The police never bothers me. I've never done anything remotely criminal, so I have never been in prison.
In some countries people are bothered by police and priests and criminals and racists and religious bigots - but AFAICS this came centuries before the data slurping. Death penalty for atheism? It cannot be blamed on Google, Apple, Facebook or Apple.
Some emergency services of hospitals need coordinated efforts at full capacity and full attention from a number of different sources now. If one computer-dependent service is crippled, that will easily influence negatively throughout the system. No med tech equipment needs to be affected: decreased availability of patient history or lab results is enough to cause delays and increase risks.
Some actually do need to access web mail during working hours, and some do need to extract or enter files on removable media. Research and teaching does not always take place on the same network as the patient records, but both are legitimate and necessary - so data needs to be moved between networks. Material has to be made somewhere, whether at work, during travel or at home. Restrictions tend to making research and teaching overly cumbersome, so there needs to be a compromise between usability and security. This is complex and requires people from different professions working together. My experience is that both IT decision makers and institution leaders ignore it.
This seems like a useless showoff of technology. If it is for morning-after diagnosis ("am I sober enough to drive?"), then saliva testing would be easier and cheaper and a lot quicker. If it is for quantifying blood ethanol during drinking, the results are likely to be _very_ variable because the alcohol needs to pass a number of barriers before reaching the detector. Even blood alcohol measured with state-of-the-art equipment is variable dring drinking. It is unlikely that a number from the instrument will be reliable, and it is unlikely that even a sober expert will be able to interpret it. So if the instrument shows a number for blood alcohol, it can only be taken to mean that the alcohol has been absorbed. No need for an instrument to show that.
These people kept secret the actual details of their technology. There was some rumour of microfluidics, and I was impressed that they seemed to have mastered this difficult art to such a degree that they could go commercial with a full repertoire and sufficient reliability to be able to deliver regularly and on time. As I understood it, they used commercial reagents in so small quantities that they could deliver results at a much lower cost. Everybody familiar with the art know for some analytes there is a systematic difference between capillary blood samples as used by Theranos and venous blood samples used for routine in most other labs. But this could easily be compensated by establishing different reference values for those analytes
I was a little suspicious, though, that people coming from a brilliant academic institution so easily could enter successfully into the mainstream of the boring everyday world of clinical chemistry. It does not happen in my part of the world.
The investors did not know that, of course. So one can understand why they did not investigate more thoroughly.
If I read the article right, acute kidney injury was the primary target. Acute injury predisposes for chronic renal failure which is a personal disaster for those struck by it. Chronic haemodialysis or renal transplantation are life saving, but are nonetheless a heavy burden healthwise and practically.
So the project of finding early warnings - and hints of why some seem to be protected - in seemingly irrelevant observations - is a laudable one. Early and effective intervention in risk groups would be a great improvement compared to the present-day situation.
Getting rid of the need for kidney transplants would be great. Someone has to start with data gathering to find clues for a work hypothesis. Google did.
No disagreement about equal rights and equal opportunities and equal pay, in all countries. Unfortunately there are feminist extremists who dominate some channels and, I am sorry to say, have poor command of their subjects. We can cope with those, even though we may have to misbehave in meetings.
But quite a few apparently moderate feminists squeeze out men from the workplace by hiring only women. So the net effect in those cases is a reversal of roles - from patriarch to matriarch. I do not think it is an improvement.
A substance, new or repurposed, is not a drug until there is sufficient knowledge about the the indication (which disease or which tumour in which patients?), effective dosing schedule(s), actual doses and duration of treatment. Buying time by partial remission is good, but complete cure is better. Studies to support generation of protocols are difficult to finance, and there are quite a few bureaucratic obstacles. Hard for all those who are not industry with their deep pockets.
Some modern treatments convert lethal diseases into chronic diseases. Quick and complete cures are less profitable for the industry and are not supported. The independent review boards might be sceptical too.
We have some other examples of anti-infectives binding to lipids - think colistin and amphotericin. None of those are highly selective towards the infective agents - they cause considerable injury to the host as well. Other peptide antibiotics exist, but their toxicity is problematic (e.g. bacitracin).
Searching for new natural anti-infectives has been a good idea for decades - but the greatest success story from the safety and efficacy side are the beta lactam antibiotics. The first representative of the group was penicillin. Numerous related substances have been developed and are extensively used. Resistance is rising because of drug-destroying enzymes produced by the bacteria (betalactamases). It is an arms race - and the complexities are increasing. But there is no reason to give up developing better inhibitors for betalactamases. Teixobactin is unlikely to be a replacement for betalactams such as penicillins, cephalosporins or carbapenems.
Non-alcoholic beers may contain up to 0.7 percent alcohol by volume. One unit will not tip you over the legal limit - even a zero litit - because there is a safety margin included in police procedures. But if I drink one such unit at lunch, it affects my alertness a lot more than it would have if I drank that or a larger amount in the evening.
Falling asleep at the wheel: Too risky compared to the pleasure of a (non-alcoholic) beer.
A reading of zero is likely to be reliable. Values around the legal limit are risky. You are then betting your driving license on full synchronisation of your instrument with those of the police.
The gadgets to avoid are the ones with falsely low readings and high variability. I suppose package inserts and CE labelling are more reliable than the most recent publication from Vulture Alcotesting Lab.
A large chunk of medical diagnostics are based on basic knowledge and simple clinical observations. A cancer needs to be surgically removed. A bacterial infection of lungs or kidneys or wounds or brain almost certainly will be best treated with one or more antibiotics. Survival may depend on startup of antibiotic treatment long before the detailed biochemical characterisation of the offending bacteria has been finished. A broken bone requires surgery or repositioning and a cast - osteoporosis may be a severe problem during surgery, but some sort of treatment is mandatory. Dementia means that the patient needs special care. Drug or alcohol abuse require detoxification and social rehabilitation.
Proteomics and genomics are mainly irrelevant to these conditions, except as research tools.
Some diagnostics require special knowledge and special skills and are not for lay people. People with well-defined chronic conditions may run their own diagnostics to detect irregularities. Diabetes patients are self-monitoring their blood glucose and dosing insulin accordingly. A person using warfarin can monitor INR with a handheld instrument - with better anticuagulant control than possible if the doctor does it. A person with recurrent urinary infections may use strips specific for leukocytes in urine when symptoms arise and start treatment earlier. A person with ulcerous colitis may test for blood in the stools much more quickly than the GP and may modify the drug regimen accordingly. Women who believe they may be pregnant, can now buy their pregnancy test in the local supermarket and act accordingly - stop drinking and smoking and eating unpasteurised cheeses, or apply for abortion.
Yes, the industries pushing instruments and reagents - and their shils - use to argue that way. There's no end to what can be cured some day in future when genomics and proteomics services are available everywhere.
There's a lot of money to be made by transforming simple procedures into hi-tech complexities. In the end the system will be unaffordable for the users.
Most ailments are easy to diagnose and simple to treat. No proteomics or genomics are required to diagnose a pneumonia or a broken leg. Or even alcoholism.
And there is a parallel development going on - enabling patients to do their own diagnostics and monitoring with small and cheap handheld instruments.
The problem is that there may be fuzzy borders between responsible and irresponsible use of substances. There can be no doubt that drug or alcohol addiction is a problem to the user, but much more to the surroundings. So there are arguments for restrictions on use and availability of recreational drugs in order to protect the innocent. Drug use is not a purely personal matter.
Opiates, whether morphine, codeine or heroin, are effective against pain and cough. The differences between them relate to the routes of intake and the number of milligrams needed for effect. But do you seriously think they are useful as recreational drugs?
Cannabis, the natural stuff, is a mixture of active substances. Some of them have rather long half-lives. It seems that they are not as innocuous as the old hippies tell us. Long-term effects seem to be real.
It seems that serious people have investigated the matter and come to a conclusion. So - who should have access to opiates and cannabis?
And how about amphetamines and cocaine?
>Targeting screen testing could prove to be far more expensive through.
Really? A patient is going to have fluorouracil for a cancer. Targeted screening will be for defects in dihydropyridine dehydrogenase
Like full genome sequencing these tests are also becoming less expensive. In a nonprofit hospital it is cheap.
>Once you map a whole person genome and can understand all portions of that genome querying which drugs is more suitable to your condition is just as simple as entering a search query
You choose antibiotics or anti-HIV medications based on the patient's genome? Or analgesics? You don't.
>You could even do simulations on how that genome will react to environmental conditions
Yes, indeed. So Google will know the contents of all your foodstuffs and all the other environmenta factors that will influence your drug metabolism and drug response and will reliably predict the kinetics to an accuracy that will make actual clinical monitoring superfluous - based on the genotyping of your receptors and signal systems and enzymes and constitution. Genomic mapping cannot replace clinical follow-up. Can Google predict renal failure from dehydration or bleeding or infection based on genetics? Even Google cannot do that.
>project tango shows that Google is working on getting new sensor measuring technology out into the world
"can actually build a visual map of rooms using 3D scanning. The company believes the combination of these sensors with advanced computer vision techniques will open up new avenues for indoor navigation and immersive gaming, among many other things."
Not relevant at all.
With Google's resources nothing is impossible. But amateurs very quickly lose their way - and those who listen to the full genome maping hype, have already lost it.
For investigating a suspicion of an inheritable disease, genome mapping can be a suitable screening tool. But most bodily diseases are caused by environmental factors: infectious agents, unhealthy diets, smoking and alcohol, injuries. In these cases standard diagnostic tools are better suited. Simply ask questions and look at the patient - and ho! There is preciously little help in genome mapping for predicting drug idiosyncrasies. When necessary, simple targeted screening will do the job more quickly, and without the privacy concerns associated with big data. Measuring drug concentrations will take care of variations caused by day-to-day variations or drug interactions. For this, miniaturized point-of-care equipment seems much more attractive than the big data monstrosity. Lots have happened on miniaturized measuring equipment, and Google pretends that it did not happen.
You might change your mind if you bought a netbook with touchscreen and Win8.1. I did (I needed a 32-bit system).
Throw out all the adware and plug in a mouse and it's Win7. The touchscreen is much nicer for scrolling and navigating.
W 8.1 gives me the best from the two worlds.
These governmental database systems are administrative databases. The real content - whatever you say - must be rather simple, even though the entire structure is complex.
I've seen a number of IT disasters from below - and I've seen the providers conning the bosses into requiring huge and complex systems for quite simple tasks. The systems are written for the bosses, and the lay users are always forgotten. They are let down with substandard tools for doing their jobs.Ever after they have to follow rigid and non-intuitive routines to mellow the aggressiveness and unforgiving nature of the final solution which could have been made much simpler, cheaper and better.
Classical or classical. I had the SR-52, the precursor to Ti59 (http://en.cyclopaedia.net/wiki/TI-59).
Read errors on the magnetic cards were a nuisance, and battery life was so-so - but space permitted me to program anovas on it. Made me a local statistics expert in the late 1970s.
The printer was very helpful for documentation purposes. There were occasional contact problems, but wriggling usually solved it.
Just a few trivial questions before I invest: Where does the energy for the smelting of ores come from? What is the plan for providing energy for feeding the 3D metalworks printer? What's the chemistry for extracting the oxidant for the fuels - and where does the energy come from? How about a pilot plant on Earth - just to demonstrate the technology?
And where is the guarantee that the dataset is correct? A full-genome sequence isn't 100 percent correct; besides it isn't complete: it's still a selection. So it is more suitable for research than for individualised treatment.
Individualised at what level? Drugs designed for that specific genotype, different from all the 280 other relevant genotypes - or just simple pre-emptive surgical removal of breasts and ovaries based on a family history and a few specific genetic tests?
How about spending a few hundred million on an effective campaign against tuberculosis - with real and effective treatment available today. Or a political decision to curb the wildest marketing of unhealthy foods.
Ah no - there's no Big Money to be made from such efforts. On the contrary.
Are they going to sequence the tumour in search of tumour-specific genetic changes? If so, it would be relevant for the disease if they found a consistent difference between some of the tumour tissue compared to normal cells. But a tumour may be heterogenous, so which data will have more weight.
This is a chemical method looking desperately for applications. The money is in the instruments and the hype and in the big data. The Next Black Hole.
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