Just thought would mention, normally for new product releases there are at least 2 distinct batches to arrive in stores.
First is air freighted typically not many units(often on pallets), second about a month later for the US, are standard shipping containers with the vast bulk of the supply. Air freighted products quite a bit more expensive (i looked at costs a couple of years ago and it was >5x).
If have just spent large $ on a production run, want to get some return as soon as possible but don't want to wreck quite often tight margins by air shipping too much and have it sit around for the month it takes the bulk to arrive. By selling out early can quite often get publicity and pre-orders to help shift the volume arriving later without having to discount the initial price too much.
Re inquirer articles - just cause the messenger wants them dead doesnt mean their message is incorrect.
The real problem is only going to show once the laptops are out of warranty as the customer will then have a choice of discarding the laptop or usually around $500 for a new motherboard. I imagine people will be quite angry.
In fact, most disturbing is that the men that engage in the most socially irresponsible behavior -- serial cheating, divorce, etc., are generally fathering many more children than those that "play by the rules." So with whatever genetic material influences behavior, we're going to find each generation a little more adulterous...
This is wrong.
Human children are very hard to raise successfully, it takes 20+ years in modern society. Children raised with 2 parents have great advantages with regard to getting to adulthood successfully and raising their own children.
Since birth control + dna testing + paternity laws + less privacy, adultery in the modern world is not so well rewarded as you might think.
Will take hundreds if not thousands of generations for this to play out.
The current theory is that humans lost their hair in order to be more resistant to parasites. You can still see this today in the large number of men(like 90%) shaving.
If the first sentence is true, surely men would have become naturally beardless and the second would be false?
It's work in progress, asian men for instance often cannot grow a full beard.
Given the ability to remove hair then it is quicker to evolve an alternative solution. The thought pattern "hairless people are more attractive, must remove body hair" which provides almost equivalent parasite protection and selection advantage as actually having no hair.
And how about that head-hair, eh? In most straight-haired people, it grows to indeterminate length, until it gets cut or strangles its bearer. Where's the evolutionary advantage of that? What a weird design. I wonder if it's a product of culture working through evolution: the the need for hair grooming is part of the social pact, keeps us in the troupe. A deep syntax of the body?
It's there to show we have been healthy for a reasonable amount of time, sortof like long fingernails. If you are female and your hair is too short it implies to potential mates that you have been ill/starving/parasite infected recently and are thus seen as less attractive.
To counteract the parasite threat, have to develop strategies to keep hair clean. Look at any modern female how many hours a week + money is spent in looking after their hair.
Many men lose their hair in adulthood, the brain also is a sensitive organ a bit of insulation from direct sunight and in cold weather would have also had its advantages.
In my opinion this is one of the most interesting aspects of this research - being able to date when we started becoming hairless. It's always been a puzzle why we are relatively hairless compared to the other great apes, and I would guess that being able to put some time constraints on it is a step toward understanding how this happened.
The current theory is that humans lost their hair in order to be more resistant to parasites. You can still see this today in the large number of men(like 90%) shaving. And women regularly removing as much body hair as possible. When looking for sexual partners humans especially men regularly preferentially choose the least body hair possible.
For women this is especially important that they must show to males that they are parasite free and able to carry a baby to full term. The hair on the head is an exception, it takes quite a bit of effort to grow, usually 12 months of healthiness for shoulder length which seems most attractive in females ie about the same time as it would take to have a baby.
Competing theories about better tolerence of heat and for greater ability to swim have fallen in popularity to the above.
Re:That's great and all, but...
on
Growing Insulin
·
· Score: 1
As I understand the history, Humalog was made exactly this way: by modifying plain human insuliin manufactured by E. Coli. I don't know about Lantus, but the chemical difference is modest, and it should be as amenable to E. Coli or safflower production to use animal insulins as it is to use human insulins.
Yeah originally the E.Coli had there DNA fiddled with so they produced some amount of regular insulin. I am pretty sure the bacterias DNA would have to be modified slightly to produce the slightly different humalog molecule. They talk only about 'purifying' phase after the insulin is produced by the bacteria.
I guess it could also be done by some kind of enzyme which converts regular human insulin.
I've actually gone with my relative to his doctor, to help him get the insulin pump set up. My relative got by for 30 years and was comfortable with the NPH/Regular he used, and I helped him do injections when he damaged his hand. Dosing and mixing his NPH was no more awkward than for the modern human insulins, and there's been no change in the size of needles used for diabetic injections in decades, long predating the availability of Lantus and similar insulins.
Look at the NPH/Lente suspension you need to careful agitate this before injecting. That is the problem - what you draw from the vial is very difficult to get the same day after day, some days you get more active ingredient(precipitate) sometimes less. That's why they do the acid solution stuff with lantus that only precipitates once injected. If lantus was also a suspension would likely also have the same variability problems.
The main problems with needles was with the larger lente insulins ultra-lente etc. and 30 or 31 gauge needles.
And no, improved glucose monitoring and control does *not* lead to hypoglycemic unawareness. According to my relative and observing him over the years when he's been really careful and when he was really careless after one of his kids died, careful monitoring helps reduce it, and careless monitoring makes it much worse. This is apparently borne out by the old glucagon response work by Dr. Santiogo's group at Barnes Hospital decades ago, where poorly controlled or longer term diabetics had less of a glucagon response to hypoglycemia. And there are actually good papers documenting this problem with the human insulins, such as those listed at http://members.tripod.com/diabetics_world/Hypoglyc emia_Unawareness_DGG.htm#05.
There is regular talk in the diabetic newgroups that if you maintain your Hba's in the 5 range for a type 1. You are going to have a real hard time detecting hypos cause your body becomes acclimatised to the level which is normal but not much above low. This is a real problem as hypo-glycaemcia can cause brain damage.
The age of the patents is an interesting point. While the patent for insulin was made available for public use by Dr. Banting decades ago when he discovered the hormone, a number of key patents for refining insulin were apparently about to expire when Lilly came out with the human insulins, assuring their continued dominance of that marketplace. Similarly, Lantus also came out and has phased out Lente, not necessarily to the benefit of diabetics or their insurance companies due to its much greater cost.
The above is how it is supposed to work though.....provided others can freely manufacture these compounds once the patents expire. There has to be some way to pay for ongoing research, diabetics paying extra for their insulins surely isnt the worst way.
Also similarly, the glucometers seem to be in a state of constant re-invention, with new patents and new designs assuring that no small company will ever succeed in entering the market on its own.
I believe walmart is selling some kind of "own brand" commodity strips.
-Robert
Re:That's great and all, but...
on
Growing Insulin
·
· Score: 1
Hello,
Bit late on this thread but anyway.....
This is complete balderdash. The ultra-fast-acting insulins, such as Humalog, are not that fast because they're human. They're fast because they're modified away from normal insulin of any species. The processing to create this could be done on animal insulins, or be engineered into this safflower approach, as easily as it is done for E. Coli insulin producing bacteria now.
The newer insulins are analogues of the regular human insulin that give them different chemical properties, the branches on the molecule have been moved around. They crystallize differently - for faster insulins thay dont crystallize at all and hence dissolve more easily into the blood stream, for longer insulins they form larger crystals which take a realtively long time to dissolve.
I dont think this can be done post process on already existing animal insulins you need to design this into the production from scratch. ie genetic engineer e-coli or these saflower plants.
Humalog is also hideously expensive compared to "regular" insulin,
There is now a similar insulin to humalog marketed by novo, with luck the competition should bring the price down a little. I think humalog is almost at the end of its patent too.
No, the big difficulty is with the mid-range or longer acting insulins. The old, animal-based, longer acting "Lente" insulins have been phased out in favor of the vastly more expensive but somewhat flatter-in-effect "Lantus" insulins.
Lente/NPH based insulins are terrible to use - they come in a suspension(the insulin is precipitated into large crystals by zinc). A suspension is very hard to inject an accurate dose and also can block the needle(need to use wider more painful needles). Many people have real trobule with the variablity in the dosing.
Coupled with the hypoglycemic unawareness some people (such as my relative)
Hypoglycaemic unawareness is nearly always due to the better control achieved through frequent blood sugar monitoring and new insulin regimes. This gets you closer for longer to normal blood sugars and your body just cannot detect the blood sugar drop as easily.
The duration of Lantus also has very little to do with it being human based, it's a modified insulin molecule and plays interesting games with its solubility and the pH of the fluid it's in to make it last 24 hours.
There is also another insulin recently introduced(Detemir) that works by binding to haemoglobin. Slighty shorted duration than lantus but much more consistent response than the old suspension based insulins.
And Lantus is flatter in its overall effects, but this is not necessarily good, since it used to be possible to juggle the peaks of mid-range insulins like NPH or Lente to match mealtimes and reduce or eliminate the need for an additional shot of fast-acting insulin with the meals.
The NPH/Lente peak was not very strong which greatly restricted the type of foods that could be eaten. Fast acting at the time of the meal to cover the the meal carbohydrates works much better(much easier to know at mealtime than 6 hours advance what you are going to eat).
Overall, the benefits of the human insulins are perhaps a reduction in allergies (which still happen with human insulins!), and a big benefit to the pharmaceutical companies like Lilly and Novolin because their patents were expiring for refining the animal insulins, and those patents will give them another 20 years of a captive market.
Animal insulins oftened contained impurities which caused many of the allergies. Modern production apparently is much better. The other problems with animal based insulins outlined above compared to analogues will likely doom them anyway.
(I believe animal insulins are still manufactured in at least the UK, India and Brazil).
So, there may be two reasons why it runs in families: a. Genetics and b. The presence of the virus in the home/family group? If your sibling gets diabetes, is it already too late to run away to avoid exposure to the virus?
Not sure if it is still current but the research i read a few years ago mentioned that the trigger virus they suspect was fairly common in the population, caused few if any symptoms and infection occurred well before onset of the symptoms of diabetes. They gave the virus a name something like 'the 96k' based on its molecular weight.
I have not seen any follow up yet. The research could quite possibly later been disproven. ie say they found many different viruses triggering diabetes or some other environmental factor.
If sometime it is shown for certain that a virus is a trigger, what do you do then? You cant provide a immunization as that would likely cause diabetes as well, its the immune system causing the problem.
Both islet cell and pancreas transplants work to cure type 1 diabetes. They aren't viable for type 1s in general at present because of the great imbalance between the numbers of diabetics and donors but they are effective treatments. They may never be viable for most - certainly pancreas transplants won't be.
Unless i am out of date the transplants both require use of anti-rejection drugs. I think these are quite expensive, have side effects and must be taken for the rest of your life.
So assuming for a second both treatements are financially the same you have a choice of taking insulin for rest of your life + side effects or having serious operation and anti-rejection drugs for rest of life + side effects.
Diabetes often causes kidney failure(excess sugar causes neurorapthy) as they have opened you up for a kidney transplant often throwing in a pancreas as well is not a bad idea as you will now have to take the anti rejection drugs anyway for your new kidneys.
So, is diabetes a viral disease that is just incredibly hard to catch and with a disastrous ending?
Er maybe sortof.
From memory: Type 1 is an overreaction of the immune system destroying the bodies own cells(see also some kinds of arthritis). There is speculation(maybe more than speculation) that the overreaction is triggered by a particular virus or type of viruses. To get diabetes you need a certain type of immune system(ie genetic) and something to trigger it the right way(ie environment).
Type 2 is more common and a completely different disease(resistance to insulin in the body rather than absence of insulin).
Check these sites, how to prevent and reverse it
The above are almost laughable, laughable if some people, too many people didnt actually believe it.
Diabetes is not a conspiracy to sell drugs, just a really bad disease.
Think about it just for a second, insurance companies pay out millions every year in treating the symptoms of diabetes, you think they are not desparate for a cure?
I am a type 1 diabetic have been for 25+ years since i was 3 years old. For my own education i have spent countless hours finding out about the disease.
Treatmented with vitamins, i mean really? Vitamins are an order of magnitude or more cheaper than insulins, if it worked you would think it would be a fairly common treatment by now....
- Robert
I have heard from several people that have had an MRI that (a) it is almost impossible to get scheduled in any reasonable timeframe for one and (b) they are 'incredibly expensive'.
So is diabetes.
I am a type 1 diabetic and it costs thousands perhaps 10's of thousands per year to manage(if you include side effects, lost opportunities etc). This will be the case for the rest of my life(hopefully 50+ years, although diabetes has a major effect in shortening it).
If it can be prevented by a series of MRI's + drugs or any other treatment for that matter that costs less than say $100k if will be economic for most pre-type 1 patients(ie children) to undertake.
It's funny to see so many Java proponents dis C/C++ and yet Java owes its very existence to C/C++. My favorite question to people that extoll the virtues of Java is "What language do think is used for the Java Virtual Machine (JVM)?"
IBM have a JVM written in java (jeode???)
Even without proof against this is still not a good argument, the stuff in C/C++/ASM or whatever compiles to an pretty much all modern
processors is just another form of p-code that is translated and executed in hardware rather than software. The only diff between x86 and bytecode or IL is that the latter were explictly designed to do this rather something forced on the chip maker to provide backward compatability.
The underlying problem for compilation to x86 assembly is that the hardware does not guarantee constant clockcycles for instructions across processor generations ie P4 is faster in clockcycles comapred to P3 for some instructions and slower for others
Hence the decision about what x86 instructions to use for optimal execution cannot be made at compile time without limiting to a single generation of an architecture
Care to point us to a credible set of benchmarks for a real application or semi-realistic application that isn't bought by Microsoft or Sun? From my own benchmarks comparing java vs C#, I see jdk1.4.2 30% faster on real applications.
I believe microsoft can veto the publication of benchmarks relating to C#(via EULA)...hence all the published benchmarks favor them.
Slashdot Mirror
Just thought would mention, normally for new product releases there are at least 2 distinct batches to arrive in stores.
First is air freighted typically not many units(often on pallets), second about a month later for the US, are standard shipping containers with the vast bulk of the supply. Air freighted products quite a bit more expensive (i looked at costs a couple of years ago and it was >5x).
If have just spent large $ on a production run, want to get some return as soon as possible but don't want to wreck quite often tight margins by air shipping too much and have it sit around for the month it takes the bulk to arrive. By selling out early can quite often get publicity and pre-orders to help shift the volume arriving later without having to discount the initial price too much.
There is a better article here:
http://www.tgdaily.com/content/view/39045/135/
Re inquirer articles - just cause the messenger wants them dead doesnt mean their message is incorrect.
The real problem is only going to show once the laptops are out of warranty as the customer will then have a choice of discarding the laptop or usually around $500 for a new motherboard. I imagine people will be quite angry.
This is wrong.
Human children are very hard to raise successfully, it takes 20+ years in modern society. Children raised with 2 parents have great advantages with regard to getting to adulthood successfully and raising their own children.
Since birth control + dna testing + paternity laws + less privacy, adultery in the modern world is not so well rewarded as you might think.
Will take hundreds if not thousands of generations for this to play out.
- Robert
It's work in progress, asian men for instance often cannot grow a full beard.
Given the ability to remove hair then it is quicker to evolve an alternative solution. The thought pattern "hairless people are more attractive, must remove body hair" which provides almost equivalent parasite protection and selection advantage as actually having no hair.
And how about that head-hair, eh? In most straight-haired people, it grows to indeterminate length, until it gets cut or strangles its bearer. Where's the evolutionary advantage of that? What a weird design. I wonder if it's a product of culture working through evolution: the the need for hair grooming is part of the social pact, keeps us in the troupe. A deep syntax of the body?
It's there to show we have been healthy for a reasonable amount of time, sortof like long fingernails. If you are female and your hair is too short it implies to potential mates that you have been ill/starving/parasite infected recently and are thus seen as less attractive.
To counteract the parasite threat, have to develop strategies to keep hair clean. Look at any modern female how many hours a week + money is spent in looking after their hair.
Many men lose their hair in adulthood, the brain also is a sensitive organ a bit of insulation from direct sunight and in cold weather would have also had its advantages.
In my opinion this is one of the most interesting aspects of this research - being able to date when we started becoming hairless. It's always been a puzzle why we are relatively hairless compared to the other great apes, and I would guess that being able to put some time constraints on it is a step toward understanding how this happened.
The current theory is that humans lost their hair in order to be more resistant to parasites. You can still see this today in the large number of men(like 90%) shaving. And women regularly removing as much body hair as possible. When looking for sexual partners humans especially men regularly preferentially choose the least body hair possible.
For women this is especially important that they must show to males that they are parasite free and able to carry a baby to full term. The hair on the head is an exception, it takes quite a bit of effort to grow, usually 12 months of healthiness for shoulder length which seems most attractive in females ie about the same time as it would take to have a baby.
Competing theories about better tolerence of heat and for greater ability to swim have fallen in popularity to the above.
Yeah originally the E.Coli had there DNA fiddled with so they produced some amount of regular insulin. I am pretty sure the bacterias DNA would have to be modified slightly to produce the slightly different humalog molecule. They talk only about 'purifying' phase after the insulin is produced by the bacteria.
I guess it could also be done by some kind of enzyme which converts regular human insulin.
Look at the NPH/Lente suspension you need to careful agitate this before injecting. That is the problem - what you draw from the vial is very difficult to get the same day after day, some days you get more active ingredient(precipitate) sometimes less. That's why they do the acid solution stuff with lantus that only precipitates once injected. If lantus was also a suspension would likely also have the same variability problems.
The main problems with needles was with the larger lente insulins ultra-lente etc. and 30 or 31 gauge needles.
There is regular talk in the diabetic newgroups that if you maintain your Hba's in the 5 range for a type 1. You are going to have a real hard time detecting hypos cause your body becomes acclimatised to the level which is normal but not much above low. This is a real problem as hypo-glycaemcia can cause brain damage.
The above is how it is supposed to work though.....provided others can freely manufacture these compounds once the patents expire. There has to be some way to pay for ongoing research, diabetics paying extra for their insulins surely isnt the worst way.
I believe walmart is selling some kind of "own brand" commodity strips.
-Robert
Bit late on this thread but anyway.....
The newer insulins are analogues of the regular human insulin that give them different chemical properties, the branches on the molecule have been moved around. They crystallize differently - for faster insulins thay dont crystallize at all and hence dissolve more easily into the blood stream, for longer insulins they form larger crystals which take a realtively long time to dissolve.
I dont think this can be done post process on already existing animal insulins you need to design this into the production from scratch. ie genetic engineer e-coli or these saflower plants.
There is now a similar insulin to humalog marketed by novo, with luck the competition should bring the price down a little. I think humalog is almost at the end of its patent too.
Lente/NPH based insulins are terrible to use - they come in a suspension(the insulin is precipitated into large crystals by zinc). A suspension is very hard to inject an accurate dose and also can block the needle(need to use wider more painful needles). Many people have real trobule with the variablity in the dosing.
Hypoglycaemic unawareness is nearly always due to the better control achieved through frequent blood sugar monitoring and new insulin regimes. This gets you closer for longer to normal blood sugars and your body just cannot detect the blood sugar drop as easily.
There is also another insulin recently introduced(Detemir) that works by binding to haemoglobin. Slighty shorted duration than lantus but much more consistent response than the old suspension based insulins.
The NPH/Lente peak was not very strong which greatly restricted the type of foods that could be eaten. Fast acting at the time of the meal to cover the the meal carbohydrates works much better(much easier to know at mealtime than 6 hours advance what you are going to eat).
Animal insulins oftened contained impurities which caused many of the allergies. Modern production apparently is much better. The other problems with animal based insulins outlined above compared to analogues will likely doom them anyway.
(I believe animal insulins are still manufactured in at least the UK, India and Brazil).
- Robert
So, there may be two reasons why it runs in families: a. Genetics and b. The presence of the virus in the home/family group? If your sibling gets diabetes, is it already too late to run away to avoid exposure to the virus?
Not sure if it is still current but the research i read a few years ago mentioned that the trigger virus they suspect was fairly common in the population, caused few if any symptoms and infection occurred well before onset of the symptoms of diabetes. They gave the virus a name something like 'the 96k' based on its molecular weight.
I have not seen any follow up yet. The research could quite possibly later been disproven. ie say they found many different viruses triggering diabetes or some other environmental factor.
If sometime it is shown for certain that a virus is a trigger, what do you do then? You cant provide a immunization as that would likely cause diabetes as well, its the immune system causing the problem.
Both islet cell and pancreas transplants work to cure type 1 diabetes. They aren't viable for type 1s in general at present because of the great imbalance between the numbers of diabetics and donors but they are effective treatments. They may never be viable for most - certainly pancreas transplants won't be.
Unless i am out of date the transplants both require use of anti-rejection drugs. I think these are quite expensive, have side effects and must be taken for the rest of your life.
So assuming for a second both treatements are financially the same you have a choice of taking insulin for rest of your life + side effects or having serious operation and anti-rejection drugs for rest of life + side effects.
Diabetes often causes kidney failure(excess sugar causes neurorapthy) as they have opened you up for a kidney transplant often throwing in a pancreas as well is not a bad idea as you will now have to take the anti rejection drugs anyway for your new kidneys.
- Robert
So, is diabetes a viral disease that is just incredibly hard to catch and with a disastrous ending?
Er maybe sortof.
From memory: Type 1 is an overreaction of the immune system destroying the bodies own cells(see also some kinds of arthritis). There is speculation(maybe more than speculation) that the overreaction is triggered by a particular virus or type of viruses. To get diabetes you need a certain type of immune system(ie genetic) and something to trigger it the right way(ie environment).
Type 2 is more common and a completely different disease(resistance to insulin in the body rather than absence of insulin).
- Robert
Check these sites, how to prevent and reverse it The above are almost laughable, laughable if some people, too many people didnt actually believe it. Diabetes is not a conspiracy to sell drugs, just a really bad disease. Think about it just for a second, insurance companies pay out millions every year in treating the symptoms of diabetes, you think they are not desparate for a cure? I am a type 1 diabetic have been for 25+ years since i was 3 years old. For my own education i have spent countless hours finding out about the disease. Treatmented with vitamins, i mean really? Vitamins are an order of magnitude or more cheaper than insulins, if it worked you would think it would be a fairly common treatment by now.... - Robert
I have heard from several people that have had an MRI that (a) it is almost impossible to get scheduled in any reasonable timeframe for one and (b) they are 'incredibly expensive'.
So is diabetes.
I am a type 1 diabetic and it costs thousands perhaps 10's of thousands per year to manage(if you include side effects, lost opportunities etc). This will be the case for the rest of my life(hopefully 50+ years, although diabetes has a major effect in shortening it).
If it can be prevented by a series of MRI's + drugs or any other treatment for that matter that costs less than say $100k if will be economic for most pre-type 1 patients(ie children) to undertake.
- Robert
It's funny to see so many Java proponents dis C/C++ and yet Java owes its very existence to C/C++. My favorite question to people that extoll the virtues of Java is "What language do think is used for the Java Virtual Machine (JVM)?"
IBM have a JVM written in java (jeode???)
Even without proof against this is still not a good argument, the stuff in C/C++/ASM or whatever compiles to an pretty much all modern processors is just another form of p-code that is translated and executed in hardware rather than software. The only diff between x86 and bytecode or IL is that the latter were explictly designed to do this rather something forced on the chip maker to provide backward compatability.
The underlying problem for compilation to x86 assembly is that the hardware does not guarantee constant clockcycles for instructions across processor generations ie P4 is faster in clockcycles comapred to P3 for some instructions and slower for others
Hence the decision about what x86 instructions to use for optimal execution cannot be made at compile time without limiting to a single generation of an architecture
Care to point us to a credible set of benchmarks for a real application or semi-realistic application that isn't bought by Microsoft or Sun? From my own benchmarks comparing java vs C#, I see jdk1.4.2 30% faster on real applications.
I believe microsoft can veto the publication of benchmarks relating to C#(via EULA)...hence all the published benchmarks favor them.