The Models Redux

Nature has an interesting piece on the models and their advocates. Before commenting one should recall the old adage: Generals make many war plans, but after the first gun has fired, they are all thrown out and actions are taken on the fly. One need look no further than the classic War Plan Orange, war with Japan, which totally missed Pearl Harbor.

So if we at times see this process as ad hoc, just look at some of our prior wars. Nothing is necessarily what it appears to be.

This gets us to models. I have a few, and I have done well over a thousand for various businesses and investments. I can assure one that reality never matched the model, never. Models do help you to think about issues but ultimately there is always the "Oh s..t" moment. That is when the war usually begins.

The Nature piece states:

Governments across the world are relying on mathematical projections to help guide decisions in this pandemic. Computer simulations account for only a fraction of the data analyses that modelling teams have performed in the crisis, Ferguson notes, but they are an increasingly important part of policymaking. But, as he and other modellers warn, much information about how SARS-CoV-2 spreads is still unknown and must be estimated or assumed — and that limits the precision of forecasts. An earlier version of the Imperial model, for instance, estimated that SARS-CoV-2 would be about as severe as influenza in necessitating the hospitalization of those infected. That turned out to be incorrect. The true performance of simulations in this pandemic might become clear only months or years from now. But to understand the value of COVID-19 models, it’s crucial to know how they are made and the assumptions on which they are built. “We’re building simplified representations of reality. Models are not crystal balls,” Ferguson says.

Frankly and in my opinion based upon my experience the Ferguson model is not only incomplete, ineffective but as I have noted previously reckless.

The key to any model here is understanding the transmission mechanism. It is fair to say we really do not yet have a grasp on it. Face masks not withstanding, is it a virion transmission of some form from an infected individual to an uninfected one. This virus grows at 37C which means not the nose but the lungs. There  ideas that it may get to one's face and then actually move by some heat sensing mechanism. That is one of a thousand tales.

It is critical to understand this mechanism and any model without a clear well accepted mechanism is a waste of time and yes indeed reckless.

NJ 2020 04 03

New Jersey numbers are getting worse. Despite the isolation they seem to be spreading with little to no control by the authorities.

The above is the growth in total numbers. Well above 25,000.

The above is the day to day growth. It was as low as 13% but now is approaching twice that number.

The above is the doubling time for the County per day. Smaller doubling times means faster growth. The county is now below 4.0

The above is doubling time by county. Almost half are 4.0 or below. This is now after two weeks of effective quarantine. Only one county is above 6.0 and Ocean is almost at 2.0 which is very aggressive growth!

The above is the state doubling time in days.

Above is the town doubling time. It is still above 5.5 but decreasing. The question is source of infection and the possible Typhoid Mary factor.

The above is towns in the county showing great disparity.

NJ 2020 04 02

As expected the incidence continues to grow.

However the daily percent change is below 20% and seems to be decreasing.

The doubling time per county is above. Union is below 4 days as are some smaller counties with small numbers. Note that they are all below the Academics predictions of 2.5 days.

The doubling time for Morris is holding above 4.0.

The town of Florham Park is well above 6.0

The incidence per PoP by some key towns by day is shown above. Part of the County problem is reporting consistency.

Again, the Academics model is still a Three Card Monty, they hold the cards and tell you the answer. That is reckless in my opinion as well as grossly unprofessional.

More on Doubling

We also are tracking per county doubling time. Below are the times per county for today.

And here is Morris over time.

Note that Morris now has well above 6 days doubling. That means the Academic model of 2.5 is not even close. I wonder if the folks using that model have at least driven down to county. I would drive down to Zip code. That is what real honest epidemiologists would do. Now six plus days means that by 15 April we have four time the number not 50! Opps......

NJ 2020 04 01

The total numbers keep increasing.

The daily rate of change is still below 20%

Which gives a doubling time above 4. This is well above the 2.5 leading to the 200,000 projected by the Academics.

The above is the per county numbers in total.

The above is the county percent daily change.

And above the changes allocated by County.

I Like NK Cells

Natural Killer cells are part of the innate immune system. They are often one of the first to attack invaders. CIK cells are enhanced NK cells that have been shown effective against MDS. Now we have CAR NK cells.

As reported in Cancer Discovery:

Nearly 3 years after showing, preclinically, that natural killer (NK) cells outfitted with a chimeric antigen receptor (CAR) could be a promising alternative to CAR-bearing T cells, the first clinical data are in from researchers at The University of Texas MD Anderson Cancer Center (MDACC) in Houston. It’s early days, but “that we’ve seen responses even during phase I is very encouraging,” said senior author Katy Rezvani, MD, PhD. She and her team published results from 11 patients with relapsed/refractory non–Hodgkin lymphoma or chronic lymphocytic leukemia who received CAR NK cells targeting CD19.... These cells, also equipped with the IL15 gene to improve proliferation and survival, were derived from MDACC’s umbilical cord blood bank—unlike T cells, NK cells do not cause graft-versus-host disease, and a donorgeneric product can be safely administered. The objective response rate was 73%, including seven complete responses. Notably, none of the participants developed cytokine release syndrome or neurotoxicity, two common complications with CAR T-cell therapy. “I believed we’d see efficacy,” Rezvani observed, “but the safety profile is really beyond what we could have expected.” Phase II of the trial is under way; a global study is also being planned with Takeda.

 These are powerful immune cells and enhancing them with CAR receptors cal allow for more aggressive treatments.