Etiquette



DP Etiquette

First rule: Don't be a jackass.

Other rules: Do not attack or insult people you disagree with. Engage with facts, logic and beliefs. Out of respect for others, please provide some sources for the facts and truths you rely on if you are asked for that. If emotion is getting out of hand, get it back in hand. To limit dehumanizing people, don't call people or whole groups of people disrespectful names, e.g., stupid, dumb or liar. Insulting people is counterproductive to rational discussion. Insult makes people angry and defensive. All points of view are welcome, right, center, left and elsewhere. Just disagree, but don't be belligerent or reject inconvenient facts, truths or defensible reasoning.

Tuesday, May 5, 2020

Time to play that "Who should Joe Biden pick as VP" game.

OK FOLKS:
I hope I don't get too much grief over some of my comments below, but my opinions are MINE, and I would still like to hear YOURS.

As we are figuring out, Biden desperately needs to make a wise pick for VP, someone who is passionate and can sock it to Trump, but also articulate (which Biden isn't), and someone who will appeal to a broad range of voters.

ALAS, he made a commitment to select a female - which might be a good idea since there are some awesome female leaders out there - but also some awesome male leaders (AndrewCuomo).

SO let me get the ball rolling:

My choices AND why or why not:

Let me first address the elephant in the room - should the pick automatically be a woman of color?
NO (as it shouldn't be automatic)  - but considering there are some damn good ones out there, maybe?

IF it has to be a woman of color, no to Stacy Abrams or Kamala Harris (Abrams too dull, Kamala too angry), but here is a name for you - Atlanta Mayor Keisha Lance Bottoms


She checks off all the boxes: articulate, strong-minded, passionate, and yes, being attractive helps (this is America after all) 

NO - NEVER to Hillary Clinton, but I would support the pick of Elizabeth Warren 


Two reasons: she would help bring in the progressive vote AND she would drive Trump absolutely bonkers (OR should I say - more bonkers than he already is) 

I would also say no to Gretchen Whitmer but if Biden wanted to draw more of the Hispanic vote, why not Catherine Cortez Masto?


Again, she has popular appeal, is well spoken, and would bring passion to an otherwise stale Democratic ticket.

OF COURSE, my #1 choice would be:


NOW YOUR TURN FOLKS:

Who would you pick - or not pick - and WHY?








Monday, May 4, 2020

UTILITY AND ALL THAT! Part 2.

Arming You to Fight Mainstream Economic Theory by Reconstructing It Into What It’s Properly About--by Larry Motuz
Given the comments I’ve received so far, some have ‘read into’ what I’ve said about objective benefits from the uses of goods, a.k.a. value-in-use, as an attempt to introduce ‘morality’ into economics. I have no intention of doing so. I have every intention, however, of re-introducing objective utility back into economics. Objective utility is an always measurable, well-defined unit of benefit obtained when we use goods.

We buy goods to use them to obtain what benefits their uses can and do provide to us. We buy foods to eat for their nutrients we obtain when we eat them. We often also get some pleasure/subjective satisfaction when doing so. That acknowledged, we must not confuse the possibility that we might some pleasure or satisfaction with always having gotten some pleasure or satisfaction because that we obtain nutrients when we eat foods.

(That's why I previously mentioned George H.W. Bush being mightily unsatisfied if he had to eat broccoli!)

Now if we are producers-who-consume :: And consumption is the use of goods we purchase/rent/lease buy to use/employ to get well-defined, objectively measurable benefits and possibly also some satisfaction in doing so :: that term neither means nor implies that we don't have subjective preferences or that these never metter.

We do have preferences. Heaven knows we have our likes and dislikes. Mostly, when we can afford to, we try to obtain benefits in ways we prefer to. But when we cannot afford to, we 'make do'. Benefits and benefit levels matter more to us than our preferences do when we 'make do'.

Mainstream (a.k.a. orthodox) economics says that ‘rational’ people would never buy any amounts of anything which they got no pleasure or subjective satisfaction from. Indeed, a consumer cannot 'maximize' subjective satisfaction above all else if s/he 'behaves' contrarily. That would be, er, 'irrational' behavior according to the Theory of the Consumer.

But that assertion rests upon confusing realizing pleasure or satisfaction with obtaining objective benefits. That confusion has seriously undermined the development of economics as a 'science'.

I'll note here that people are not the only actors in economic systems. Organizations are also actors.

These are ‘fictive persons’ that are economic actors. If 'for profit', these actors consume/employ goods with one objective particular benefit in mind: "profits" (measured in currency units).

These do not choose what they consume/employ on the basis of their subjective preferences between goods. 'Fictive persons’ have no ‘subjective preferences’. Which is not to say that those in charge of such 'fictive persons' are unable to exercise their particular preferences. If these can do so without costing the 'fictive person' --read a for-profit Corporation here-- much if anything, their shareholders will be happy to let them do so. And, given cultural values, other 'values' may come into play also.

But usually it's fair to assume theoretically that ‘fictive persons’ use ‘goods’ they choose on the basis of their cost and their respective contributions/usefulness as inputs into their production. A ‘for-profit’ corporation hardly buys a computer because it subjectively ‘prefers’ to have one over having, say, accountants or other workers. It does so mainly because using/employing a computer in some operations cuts the costs of those operations. It makes financial sense to buy a computer when that computer and its maintenance costs can be recovered or more than recovered when it's employed. [And, not to put too fine a point on this, there is also benefit in having a computer which never tires or argues back relative to workers who do both.]

Producers-who-consume is a term I use to include all economic actors.

In my unfolding framework, the term replaces the notion that some actors --people and only people-- are the only ‘consumers’ in economic systems. The term challenges the idea that others are the only ‘producers’. The term means that all actors use goods to obtain benefits from those uses. And that means that a proper Theory of the Consumer cannot exclude any economic actors.

If we are all producers-who-consume, buying goods and using them with regard to both objective and subjective benefits which we hope or intend to get,then we need new framework for economic theory and analysis. Constructing that is my objective. And, it is my only objective.

We know that a business must earn enough to cover its fixed plant and capital costs and the variable input and maintenance costs of what it employs to make what it sells. Unless it covers its costs though revenue generating sales streams, it will operate in the ‘red’,underwater as it were. Without access to other finances than sales revenues, it may be unable to remain in business over time.

It would be absurd to hear a CEO say, “We’re losing money hand over fist in our operations and we expect to continue to do that, but, if we ignore this as merely incidental to our welfare and continued survivalas a business,well, then take it from our staff economists that we’re in greatest shape we could be in given our very strained circumstances. They tell us we've rationally done everything in our power to keep running/alive, so, by that measure :: that we're still here despite everything! :: we've maximized our welfare. [That’s one among the many reasons business schools tend to burst out in hilarious guffaws when hearing what economists say. {*An exception to this is Engineering Project Management. This is effectively a sub-discipline within economics usually taught by Engineers to Engineers. It neither needs nor uses the economic Theories of the Consumer or that of the Firm.}]

Why should we accept any such statements when they are applied to people when talking about them having maximized their welfare?

Do not people have bodies? Do they not have to cover the costs of their operations? Do they not have to maintain themselves?

These are not moral questions whatever the answers. And "Yes", they have bodies and must replenish what they use to maintain themselves.

To be sure, they both are and have bodies which cost them nothing to get. A business must buy, rent, or lease a plant out of which it operates, so people are different in that regard.

However, both sets of actors face variable ‘costs’ associated with maintaining their 'bodies' and continuing their 'ongoing operations'. What people's bodies metabolically use up needs be replenished.

If a business dips into savings or uses its ongoing sales revenues to do so, people also do so.

For most people most of the time, their income is what they earn when they sell their time and skills to employers.

So, if, say, I need 80 units of protein daily to maintain my health and life, then that is an Exigency requirement (ER) which I must meet. Should I only manage to afford to obtain only 40 units daily over any significant period, it cannot be said that I am doing well. Protein shortfalls/deficiencies lead to diseases over time, eventuating in death. Neither disease nor death, at least to me, is equivalently 'doing well'.

Let's now generalize. Let’s say we label what a person gets to obtain daily as (G). That’s all they manage to Get (G) in a period. We can now create an Index of Utility because we know the Exigency requirement (ER).

We'd do so by using the formula t*(G-ER)/(t*ER)[where t is the length of the period in, say, days] to create a simple Index of Utility. If t*(G-ER) =0 then so does the Index Measure. That's good.

Any index value less than zero over a significant period of time period leads to health decrements. If the period is long enough, that can mean lifetime disease, disability and/or death. So, Utility Indices less than zero could indicate poor physiological well-being if we're looking at lengthy periods over which this shortfall is happening.

If the index is greater than zero, well how much greater matters? Gout,for example, is one disease which may result if one consumes too much protein over a significant period. (There are other diseases associated with overmuch protein consumption.)

Which is to say that more is not necessarily better. There’s usually a range of nutrient consumption which we can define as relatively good. It's sandwiched between other ranges that are ‘bad’.

I don’t think it’s a task of economists to tell anyone if s/he is consuming too much of anything: that too much is bad specifically for them. A doctor perhaps, but not an economist.

But should it not be a task of economists to develop useful indices of well-being or welfare?

Similarly (but not identically) for a business, if GSR is sale revenues (SR) received/gotten (G) in time period t, and if, say, in a quarter, its sales revenue target is ExigencySR (ESRt)to cover its fixed and variable costs, then we get (GSRt -ESRt)/ESRt as an Index of Covered Costs. An index value of Zero will be ‘good’ because costs have been covered. Profits always being desirable to businesses, more than Zero is better, for there’s no upper range where profits ever become excessive: I.e., ‘bad’ for them. An index value above is gravy. [Just like people can't have too much money --they'll take more if someone offers to give it to them--businesses can never have too much profit.]

That said, in yet other respects, businesses are like people. They do not want inventories of inputs piling up, for storage costs can become very costly to business. Just like an excess of proteins for an individual, an excessive supply of inputs can become harmful to a business. Though more money is never 'bad', more input than needed can be.

I've no doubt whatever that businesses use far more sophisticated indices, measures and algorithms for keeping track of inputs needed for the production capacity utilisation warranted by anticipated/hoped for market revenues. My purpose here is simply to illustrate that economists have no measures at all to indicate when too little is too little or too much is too much. Getting ahead of myself here, they have confused a singular characteristic of monies :: Namely that more is always better to have :: with this being a property of 'goods'. [They've done so due to the fact that, in monetary economies, goods can be exchanged for money. Ipso facto, more goods has become better (as long as there aren't substantial transactions costs associated with turning that 'more goods' into 'more money')!

Indices of objective utility don’t exist in orthodox economic theory. Instead, human welfare is taken to be an entirely subjective matter, and, being subjective --in the mind of the ‘consumer’ so to speak-- are beyond direct, objective measurement.[See Note 1 below for what a scientist has to say about the measures they do use for 'utility'.]

That problem lies not only in ignoring a significant and measurable part of what we obtain when we buy goods to use them in some way/s, but also in how ‘utility’ has been cast in orthodox theory as being ‘subjective preferences’ in the minds of ‘consumers’ who are never treated as ‘producers’.

That’s not to say that subjective preferences don't ever matter. Conspicuous consumption, at least in Thorstein Veblen’s sense of displaying how wealthy one is to those less wealthy and merely eking out their existence, has bio-psycho and cultural roots and benefits.

It’s rather to say that even though objective benefits can pale before the a person's psychological motivations/pleasures in some purchases, we cannot simply ignore objective benefits by only emphasizing such subjective preferences. Indeed, though a house always serves as a shelter, there are many other other factors which go into purchasing houses. Some are subjective: the status and prestige of owning a house in a ritzy neighborhood for example. Others are more objective in their dimensions: distance to and quality of neighborhood schools; ready access to rapid transit/transportation systems; to mention only two.

I've focused attention on objective benefits because the analysis of objective analysis is completely absent from the Theory of the Consumer. Not only is there no attempt to measure the values-in-use which goods provide us, some notable economists have be painstaking in their denials of such things as measurable values-in-use. Take George J. Stigler, for instance, and his famous article “The Development of Utility Theory 1” {See;http://kisi.deu.edu.tr/sedef.akgungor/Microeconomic%20Theory%201%20Fallm2009/stigler.pdf}

Stigler criticized Ricardo in this way:
Ricardo says that, if a person receives two sacks of corn where formerly he received one,"he gets, indeed, double the quantity of riches--double the quantity of utility-- double the quantity of what Adam Smith calls value-in-use." Hence, he did not believe that marginal utility diminishes as (total) utility increases. ((Total) added by me for clarification.){Note:This means that increments to total utility fall as more and more of a good is acquired, so the rate of change of total utility is always falling.]

And Stigler, after quoting yet another statement he disapproves of, he goes on to say "The writer of this passage [Ricardo] cannot be said to have been close to the notion ofmarginal utility" [That’s the notion that increments to total utility grow become ever smaller less as more and more of a good is consumed.]

And I have to acknowledge that Stigler was absolutely right about Ricardo not having grasped the idea that the rate of change to total utility falls as more units of a good are purchased.

But why would Ricardo or anyone choose to believe that?

Imagine you said to your local jeweler that it made you sad to learn in your economics class that the ‘law of diminishing marginal utility' meant that he could only make ever smaller total amounts of jewelry out of his second and late acquisitions of gold/silver ingots at market prices compared to what he could make from from the first one he acquired.

He'd rightly wonder if you were daft! Imagine him puzzling:
”Why do economists say that? I’m sure I always make the same amount of jewelry with the last gold/silver ingot I bought as I do with the first. Each ingot has the same unit weight of gold/silver. Why shouldn’t one be as equally useful to me as another? I’m awfully sure that if I have 10 ingots of equal weight, I can make 10 times the amount of jewelry than I can with one.The total utility of the first ingot is not greater than the last.”

Stigler's problem with David Ricardo, Adam Smith, and other classical economists of the 18th and 19th centuries was due to one thing. Twentieth century trained economists like Stigler had absolutely no idea how important it was to distinguish between values-in-use and values-in-exchange. Somehow, so caught up have they become with values-in-exchange ::I.e., the money prices of things :: that they’ve lost all awareness of the values in-use of things. They’d graduated from their classes having learned the prices of everything and the values of nothing-at-all.

As Ricardo said, the person with two sacks of corn as wages has twice the benefit as before with only one. That is so whether s/he uses them as food (for their nutritional value as food) for the rate of change of nutrients per unit ‘bag’ do not decline as the numbers of bags acquired grows. Nutrient levels per unit measure do not fall as more unit measures are acquired, nutrients levels being equal per unit measure of corn. Constant returns per unit acquired,not declining ones, are more the rule. And should s/he sells both bags for money, or if s/he keeps one and sells the other, s/he is obviously twice as better off with two bags than with only one.

And for you to understand how this happened, I will have to show what happened and why.
'Nuff for today.

{Readers: I’d hoped to deal with ‘utility’ in only two sections. Comments on Part 1 made it very clear that I could not leave utility as quickly as I wanted to. I’d have have to add a Part 3 about how it came to be thought that prices --values-in-exchange-- became associated with the intensities of the desires a person had for goods. ‘Demand’ curves and prices ‘consumers’ were thought to be ‘willing to pay’ flowed out of such thinking, as did notions that consumers generally were able to ‘buy’ goods in markets for less than they would be ‘willing to pay’. If so, consumers generally get more ‘value’ in markets than they pay for. That’s so if but only if it is the case that they would have been willing to pay more than the ‘market’ requires them to pay… something economists call ‘consumer surplus’. I intend to produce Utility and All That Part 3 next.}

Note 1. I refer more mathematically and technically minded readers to On Ordinal, Cardinal, and Expected Utility by Jonathan Barzilai, a respected Canadian Engineer. He has very persuasively argued that economic measures of utility (and the welfare which emerges from such measures) lack all meaningful definition. Though he doesn't use my term 'mathemagics' for what economists do when misusing mathematics, he might as well have. There are numerous Internet websites which have this publication.



Links to prior posts on economics:

Analyze me...


Monday, May 4, 2020
 
I will readily admit I’m biased toward the Democrats.  Their agenda/platform more aligns with my political mindset.

As a progressive liberal, I watch MSNBC and CNN to get my news.  I rarely watch Fox, nor do I listen to right-wing radio pundits like Rush Limbaugh (I can only take about 5-minutes of him before I have to turn it off).

Here’s question 1:
-Do you see right wing media as a help or hindrance to the greater American society?  Explain your choice.

Myself, I see them as a hindrance and instigaters of anger, hatred, resentment, discord, and any other words of disruption

Here’s question 2:
-Am I wrong?  Am I not seeing things clearly through my skewed-liberal eyesight?

Lay it on the line for me.  Is it me, and not them?  Be honest.  I can take it.  Or as I like to say, “Sometimes you do someone a favor when you tell them they have bad breath.” :/

Help me understand so I can grow. :)

Thanks for posting.

When Personal Rights Collide with Social Well-Being

Context
A personal interest in politics is looking at how individuals and groups deal with situations where personal rights collide with the rights of other individuals, groups and society as a whole. My approach has been to look at various affected people and groups individually and/or society as a whole. The point of looking at affected people and groups is to try to get an at least semi-objective feel for (1) how much of a burden on rights that (i) a new social situation, (ii) a new law or regulation, or (iii) a new imposition of existing government power imposes on adversely affected people, groups and/or society, and (2) how much of a benefit accrues to affected people, groups and/or society. The analysis tries to be ideologically and morally neutral or blind, socially realistic and objective in assessing benefits and burdens.

The two detailed analyses I've done so far focused on burdens and benefits of legalized same-sex marriage (SSM) in two contexts. The first is SSM burden and benefit on freedom of religion and speech (that analysis is here). The second is SSM burden and benefit on freedom in commerce (that analysis is here). The two analyses are very different because the groups and their sizes differ and because the size or severity of impacts are often quite different. The basic lessons from those two analyses are:

1. With some exceptions, most people who complain that their freedoms and rights are burdened (~90%) tend to grossly overstate the seriousness of the burden they actually experience. Most rarely acknowledge that any expanded freedoms or rights for benefitted people and groups even exist. If acknowledged at all, the expansion is usually attacked as illegal, not American and/or immoral or evil. Some see literal brute tyranny in situations were the degree of burden on themselves and people in their group is low to almost none at all.

2. Most people who benefit tend to understate the impact of the expansion of freedom and rights for themselves. Many of them seem to be almost completely silent, as if expanded freedoms for themselves or groups they identify with is shameful or wrong somehow. That perception may be skewed by the information sources I usually rely on.

Sporadic protests against state lockdowns continue in various places. This discussion superficially considers the collision between people who oppose lockdowns to slow the spread of coronavirus and states who impose lockdowns in the name of public health. At the rate I do it, a complete analysis would probably require about 30-60 hours. As explained below, a coronavirus analysis is much more complicated than SSM analyses.


Protests against coronavirus lockdowns: 
Freedom of movement and commerce vs public health
 In theory, everyone in society can be infected and experience effects that range from undetectably mild to death. People over the age of 65 face significantly higher risk of death. The death rate is uncertain because there is insufficient testing to know what it is. So far, there has been about 68,000 deaths in the US, with the total possibly reaching at least 100,000 in the coming 4-6 months. The efficacy of lockdown measures, including wearing masks, is uncertain. The slow, inept US response may have neutered state efforts to reduce infections. Compounding the federal failure, are states that refused to impose lockdowns, possibly making unrestrained virus spread nearly impossible to stop. In view of the uncertainty of ultimate deaths, the death rate and the economic cost-benefit of lockdowns, specifying economic and public health benefits are hard to objectify. One can make uncertain estimates at best.

In terms of rights and freedoms, economic freedoms and freedom of movement burdens here are moderate to high for various groups. Some people will lose their jobs permanently or for months, possibly for years. Some or many of those people will lose their homes. The US debt will increase by trillions. The added debt will probably be about $8 trillion in the next year or two, maybe significantly more. That will probably exert negative effects on social spending such as food stamps and welfare, which in turn will have a range of adverse effects on affected groups.

As seen in other contested situations, some see outright illegality and tyranny in the burdens the lockdowns impose.







As with SSM opposition, lockdown opposition focuses on lost freedoms of burdened people and groups. Protests are usually mostly or completely silent about social benefits, such as not spreading infections to vulnerable people. Protestors see themselves as free-thinking and patriotic.



Compared to actual tyranny in places like North Korea and China, an allegation of tyranny here is an exaggeration. Compared to pre-lockdown America, the burdens on individuals are moderate to high. Moderate for people who do not lose their jobs or homes, but high for people who do lose a job and/or their home. Some families will be devastated and irreparably broken. Those costs are real and not trivial.

Some lockdown opponents are openly defying and even mocking the use of masks as a means to reduce the spread of the virus. The efficacy of masks is unknown, making mockery easier but not rational.


Because the pandemic has been politicized, the lockdowns are adding to polarization, which is socially damaging. Polarization cements existing social distrust and ill-will while fomenting new distrust and ill-will. It is hard to pin that kind of damage down, but it is not trivial. Also, the politicization is accompanied by misinformation and lies that distort the reality of the situation. That tends to inflame emotions and thus irrationality. There is social damage in all of that. Some of it is overtly threatening violence, despite being labeled with deflecting euphemisms (lies) such as being heavily armed in public for 'added security'.

 





Some of the protests make valid points. For example, some freedoms probably do not pose a risk of spreading the virus. It is likely that restrictions on those activities are going to be relaxed fairly soon. But even there, false information is sometimes mixed with valid criticism.


 That the pandemic has been politicized for the president's re-election is also polarizing and thus socially damaging.



A healthcare provider trying to make a point, 
but probably failing

Given the uncertainties, the cost-benefit of the lockdowns so far is hard to estimate. As this issue continues to polarize and divide Americans while inflicting major damage on our economy and and adversely affected people, it seems that America probably should ease restrictions in stages with advice from experts. It is hard to shake the feeling that since the federal effort failed due to a too slow and far too incompetent response, there may be no choice but to relax lockdowns fairly soon. One can only hope that the remaining uninfected vulnerable people can somehow be protected, but that seems unlikely.

We may have reached a point where American society more or less abandons those vulnerable to the virus to those who are vulnerable to the economy. What an awful situation we are in. What an awful choice.

Saturday, May 2, 2020

Some Information About Remdesivir


Short summary
Remdesivir is a moderately potent anti-viral drug. In clinical trials to test safety, the drug appears to be reasonably safe and well-tolerated. The data on whether it can decrease the death rate shows it does not do that. But what the data does appear to show, and this needs to be confirmed, is that the drug significantly shortens the time it takes a person to recover from the infection.

What remains unclear to me are (i) what "recovery" from the infection means, or how it is defined, and (ii) how early in the infection the drug needs to be started for it to have enough time to have a significant beneficial clinical effect. If the drug is started too late in a person's infection, it cannot save them if they are going to die with or without the drug.


Short technical summary
The FDA gave emergency authorization to use Remdesivir to treat the Covid-19 infection. Stories in the news yesterday indicated that some strange things had been going on in the process of authorizing use of the drug. One strange thing was a change in the 'clinical endpoint' for the drug from a reduced death rate to a reduced time to recovery, which went from 15 days to 11 days. That reduction in time to recover was called 'significant'. In drug development, 'significant' almost always means statistical significance of p < 0.05 (p means probability).

The p < 0.05 statistic means that there is a 5% chance the observed efficacy of the drug is a fluke or a false positive. A p < 0.05 value is only a modest showing that the drug is active in whatever clinical test it is analyzed in. It is preferable to hit a p-value of  0.01 or lower to have greater confidence that a drug's observed clinical activity is real.

In vivo: an assay or test in an animal or human

In vitro: an assay or test not in an animal or human, typically in cells growing in tissue culture or in cell extracts or artificial assays for individual enzymes

A February 2020 paper in the journal Cell Research reported basic antiviral activity and in vitro toxicity data for remdesivir. The drug returned values of EC50 = 0.77 μM; CC50 > 100 μM; SI > 129.87. That indicated a moderately potent drug with a relatively low toxicity profile in vitro.

The EC50 = 0.77 μM value means that at a concentration of 0.77 micromolar (μM), the drug inhibited viral replication by 50%. The EC50 is the half maximal effective concentration the drug shows in an assay. EC50 = 0.77 μM means that remdesivir is moderately potent in this particular assay. Drugs with an EC50 of 0.1 μM or lower are usually preferred.

The CC50 > 100 μM value refers to the concentration of the drug needed to kill half of the cells used in the assay. It is a general indicator of how toxic the drug is. In this case, the cells used were epithelial cells from monkey kidney. The cell line is called Vero E6 and it was developed in the 1960s. Thus, a drug that is not very toxic will have a high CC50. The lower the CC50, the more toxic the drug is. A CC50 of > 100 μM indicates that remdesivir is moderately toxic for Vero E6. It does not provide detailed information about how toxic remdesivir would be in humans.

Clinical trial experience with remdesivir in humans indicated a fairly low toxicity:
"Intravenous infusions in previously phase I clinical trials have good safety and pharmacokinetic properties. Also, no cytotoxicity, hepatorenal toxicity, or no serious adverse reactions related to metering have been observed in climbing experiments. Subjects were tolerant in studies that repeated 150 mg intravenously daily for 7–14 days. Remdesivir did not show any renal injuries in a multi-dose study."

The selectivity index value, SI > 129.87, is just EC50 ÷ CC50 (0.77 μM ÷ 100 μM). The higher the SI, the better the efficacy vs safety profile for the drug is in the assay used. Since remdesivir is not very water soluble, the CC50 is expressed as > 100 μM instead of = 100 μM. The real selectivity index cannot be evaluated due to the low water solubility for remdesivir, but it is likely to be higher than 130. However, since the SI is for an in vitro assay, it is not nearly as important as the reported toxicity and efficacy data obtained from controlled human clinical trials.

Remdesivir is a ribonucleotide analog that the virus uses to replicate itself and by incorporating the molecule into viral RNA and stopping complete duplication of the viral genome. The similarity of the remdesivir structure to natural ribonucleotides in essence "tricks" the virus polymerase into using it in place of real ribonucleotides that are always present in human, animal and cells of other kinds of self-replicating life, e.g., plants. This is a chemical strategy that has been used against RNA viruses for decades, including the first analog used to treat HIV, AZT (azidothymidine), back in the 1980s.


Remdesivir











Friday, May 1, 2020

Vaccine Risk Shift to Taxpayers

Context
When drug makers ramp up drug or vaccine production before clinical trials and data analyses are complete, it is called “at risk” production. The risk lies in the FDA’s refusal to approve the drug or vaccine on safety and/or efficacy grounds. All drug and vaccine production is usually costly, so the risk tends to be high. Companies tend to hesitate to produce at risk unless they are confident about their safety and efficacy data. The upside of at risk production is that once FDA approval is received, product sales can occur almost immediately after approval. Each day of sales protected by either market exclusivity or patents is precious. Each day can be worth millions in profit to a company.


Risk shift
The Washington Post reports that under a federal government effort, called “Operation Warp Speed”, taxpayers will assume the risk of at risk production of Covid-19 vaccine. That seems like a dumb name. Maybe the president dictated it. It sounds like him. Whatever.



Operation ludicrous speed

The downside is that taxpayers will have to pay the cost of at risk production if the vaccine fails to be sufficiently safe or effective. The upside is that if a vaccine does get FDA marketing approval, it can be at least fairly widely available within a few weeks. The goal of the effort is to have a vaccine publicly available by January of 2021. If that timeline pans out, it would be an amazing research and production achievement in such a short time.

The risk shift to taxpayers illustrates a key aspect of America’s for-profit healthcare system. Namely, it is a for-profit industry. Companies will not take risks that do not pass muster with internal company reviews, even if the risk could save many lives. Taking excessive risk can open a company and its executives up to shareholder lawsuits. Shareholders hold shares to make money, not to make people safe. That is the cold, hard reality of American healthcare. Profit, not service to the public interest, is the overwhelming moral imperative of capitalism.


Incoherent, self-serving drivel from our endlessly blame-shifting Blitherer-in-Chief
Naturally, the president chimed in. WaPo writes:
“President Trump said it is not too optimistic to try to produce roughly 300 million doses of vaccine in eight months, enough for the entire country.

‘No, I’m not overpromising. I don’t know who said it, but whatever the maximum is, whatever you can humanly do, we’re going to have. And we hope we’re going to come up with a good vaccine,’ the president said at the White House.

He added that ‘we’re going to fast-track it like you’ve never seen before, if we come up with a vaccine.’

Asked who is in charge of the effort, Trump said he is. 
‘I think probably, more than anything, I’m in charge. And I’m the one that gets blamed. And I get blamed anyway,’ Trump said.”

“I don’t know who said it.” That pretty much sums up the president’s grasp of things like science, the Covid-19 pandemic and reality in general.

“I think probably, more than anything, I’m in charge.” Probably in charge? Har, har, har! He will claim to be in charge if the effort works. But it will be the fault of Obama, Hillary’s Benghazigate and/or emailgate or something like that if it fails.

Sarcasm: Russia, if you’re listening, please find the missing emails. That is where Covid-19 came from and the vaccine recipe is in there too. Ludicrous speed on that hacking, please.

The fact that the president waited this long to jump to warp speed does mean he will be blamed for the needless delay because the delay was needless and he should be blamed. Why do this now and not three or four months ago? That inexcusable incompetence-driven delay is on the president, not Barak, Hillary, Pelosi, Schumer, the New York Times hidden emails or anything or anyone else.

Even at this very late date, the president clearly does not grasp the scope or gravity of what America is facing right now. He is amazingly clueless.


A sincere wish for the future
Maybe one day, the news won’t be so endlessly bad and idiotic. Maybe one day American politics will return to some reasonable degree of coherence and some reasonable grounding in facts, sound reason and transparent accountability. I do not know when that day will be, but I hope it is very soon.