Are Bodies Cleverer Than We Think?
Because, I had a serious stroke thirteen years ago, I am on Warfarin for life to thin my blood, so that I don’t have another stroke.
INR is short for International Normalized Ratio, which diverts on Wikipedia to the Wikipedia entry for Prothrombin Time, where these is the first two paragraphs.
The prothrombin time (PT) – along with its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) – is an assay for evaluating the extrinsic pathway and common pathway of coagulation. This blood test is also called protime INR and PT/INR. They are used to determine the clotting tendency of blood, in such things as the measure of warfarin dosage, liver damage, and vitamin K status. PT measures the following coagulation factors: I (fibrinogen), II (prothrombin), V (proaccelerin), VII (proconvertin), and X (Stuart–Prower factor).
PT is often used in conjunction with the activated partial thromboplastin time (aPTT) which measures the intrinsic pathway and common pathway of coagulation.
That is very technical and complicated, but what does it mean practically?
Those on Warfarin to thin their blood are generally supposed to keep their INR between 2 and 3.
I test the INR myself with a Coaguchek meter from Roche and have done so for nearly ten years.
Every, so often, I discuss the level of Warfarin with my GP and we adjust the level accordingly.
Typically, NHS patients on Warfarin have their INR checked every few weeks.
But as I am a Graduate Control Engineer, who has written control strategies for chemical plants, I feel this checking every few weeks, is not enough.
At times, I have checked at a higher frequency.
Four times, I have had minor operations.With the first operation, I agreed with the surgeon, that I would lower my INR to 2.1 for the operation and raise it back to 2.5 after the operation.
It all went well and I repeated the exercise for the three other minor operations.
I have checked daily since about the beginning of April, before which, I generally tested on Mondays and Thursdays.
There were two reasons for the change of frequency.
- Regular storms seemed to roll in and for some reason, they tended to lower my INR.
- I also wrote Do Thunderstorms Cause Strokes?, after reading a paper from the United States about the relationship between thunderstorms and strokes.
So I took the prudent decision to test my INR daily.
Then on the 30th May, disaster struck.
My Coaguchek meter found out it had the wrong firmware and Roche implored me to change it.
But I am not a hardware person, so I was left unable to check my INR.
Luckily, I remembered a story from the 1960s about one of ICI’s chemical plants.
This plant was one of the first fully-digitally controlled plants controlled by an IBM 1800 computer.
It also ran 24 hours a day, seven days week.
So in the middle of the night, the plant operators got out all the computer printouts, which showed how the computer had set all the valves and controllers.
One-by-one they reset all the controls on the plant to the settings that the computer had used for the last few days.
Using, this computer-assisted mode the plant was kept running, until engineers could fix the computer.
On the 30th May, my INR was a little bit high at 2.9 and I was using a dosage of Warfarin of 4 mg. one day and 3.5 mg. the next.
The strange dosage was one, that I know from experiment over time produces an INR of 2.5.
My actual average Warfarin dose was 3.73 over the last thirty days and my INR, as measured most days was 2.6 over the same period.
So, I did what the engineers did on the chemical plant, kept calm and carried on.
Yesterday my son fixed the Coaguchek meter and I was able to take my first reading for 17 days. It was 2.7 and only 0.1 higher than the 30-day average on the 30th May.
I had successfully jumped the gap in the readings.
Conclusion
Most systems have an equilibrium. Make sure you know it.
£20 Electronic Ear-Clips Train The Body To Decrease Blood Pressure
The title of this post, is the same as that of this article in The Times.
These two paragraphs outline how the device is used.
A £20 device that delivers “tingling” electric pulses to the ears and can be worn at home could be almost twice as effective as drugs at reducing blood pressure, a neuroscientist has said.
Early trials suggest that wearing the small electrodes clipped to the ears for half an hour per day over two weeks while relaxing, watching TV or eating can reduce blood pressure by up to 15mm of mercury (mm Hg), compared with 8mm Hg to 10mm Hg for drugs such as Ace inhibitors or beta-blockers.
It appears the device has been developed at University College London.
Would I Use Electronic Ear-Clips To Control My Blood Pressure?
Soon after my wife died in 2007, my cholesterol levels rose.
The Ipswich Town Physiotherapist, who was a drinking partner before matches at Portman Road, recommended that I see his dietician.
She identified the following.
- My diet had changed since my my wife’s death, as I was choosing the food and doing the cooking.
- She suspected, that I wasn’t eating enough soluble fibre.
- I was eating enough fruit and vegetables.
Her solution was two-fold.
- Swap butter and other spreads for Benecol.
- Make sure, I eat, at least one small tin of baked beans every week.
Obviously, as I had been found to be coeliac in 1997, I should stay gluten-free.
I’ve seen other dieticians since and none have criticised, what she said.
No doctor has also ever said, that there is something wrong with my cholesterol.
After my stroke in 2010, I was put on Warfarin to thin my blood.
The only addition to my cocktail of drugs, was that after an unexplained collapse, I was put on blood pressure drugs.
So to return to the question I asked at the top of this section.
I may take six or seven drugs and vitamin tablets every day, but swapping one or two for half-an-hour with an electronic device wouldn’t be too much trouble.
That is, if I could tolerate the device, as I’m not keen on headphones.
But it could be an interesting alternative to taking pharmaceutical drugs.
The Problem Of Waste Plastic And Why Pyrolysis Oil Might Just Contain The Answer
The title of this post, is the same as that of this article on the Chemical Engineer.
These three paragraphs introduce the article.
One of the few technologies that can break down unrecyclable post-consumer waste plastic, pyrolysis is fast becoming a potential recycling route for companies trying to reduce their waste output.
The world produces around 450m t/y of plastic, but only 9% is recycled, with most waste ending up in landfill. Pyrolysis, which involves heating the plastic at extremely high temperatures in the absence of oxygen, breaks down the molecules to produce pyrolysis oil or gas. The oil can then be used to develop new products.
George Huber, a professor of chemical engineering at the University of Wisconsin-Madison, is leading a research team that is investigating the chemistry of pyrolysis oil and its use in polyolefin recycling.
This is a quote from George Huber
Waste plastic should be viewed as a resource we can use to make plastics and other chemicals. We should not be landfilling or burning it, we should be reusing the carbon in waste plastics.
I very much agree with what he said.
These are my thoughts.
Pyrolysis
The Wikipedia entry for pyrolysis starts with this paragraph.
The pyrolysis (or devolatilization) process is the thermal decomposition of materials at elevated temperatures, often in an inert atmosphere.
This paragraph describes the technique’s use in the chemical industry.
The process is used heavily in the chemical industry, for example, to produce ethylene, many forms of carbon, and other chemicals from petroleum, coal, and even wood, or to produce coke from coal. It is used also in the conversion of natural gas (primarily methane) into hydrogen gas and solid carbon char, recently introduced on an industrial scale. Aspirational applications of pyrolysis would convert biomass into syngas and biochar, waste plastics back into usable oil, or waste into safely disposable substances.
I came across pyrolysis in my first job after graduating, when I worked at ICI Runcorn.
ICI were trying to make acetylene in a process plant they had bought from BASF. Ethylene was burned in an atmosphere, that didn’t have much oxygen and then quenched in naphtha. This should have produced acetylene , but all it produced was tonnes of black soot, that it spread all over Runcorn.
I shared an office with a guy, who was using a purpose-built instrument to measure acetylene in the off-gas from the burners.
When he discovered that the gas could be in explosive limits, ICI shut the plant down. The Germans didn’t believe this and said, that anyway it was impossible to do the measurement.
ICI gave up on the process and demolished their plant, but sadly the German plant blew up.
I would assume we have progressed with pyrolysis in the intervening fifty years.
University of Wisconsin-Madison
The University of Wisconsin-Madison is a top-ranked American University and is part of my daily life, as the Warfarin, that stops me having another stroke was developed at the University in the 1940s.
Conclusion
The article is a must-read and I feel that my past experience says, that George Huber and his team could be on to something.
I wish them the best of luck.
Application Of Control Engineering Principles To The Calculation Of Pharmaceutical Drug Doses
Today, I was asked by an eminent cardiologist to give my opinion on this scientific paper in the Journal of the American Heart Association, which was entitled Personalized Antihypertensive Treatment Optimization With Smartphone‐Enabled Remote Precision Dosing of Amlodipine During the COVID‐19 Pandemic (PERSONAL‐CovidBP Trial).
This was the background to the study.
The objective of the PERSONAL‐CovidBP (Personalised Electronic Record Supported Optimisation When Alone for Patients With Hypertension: Pilot Study for Remote Medical Management of Hypertension During the COVID‐19 Pandemic) trial was to assess the efficacy and safety of smartphone‐enabled remote precision dosing of amlodipine to control blood pressure (BP) in participants with primary hypertension during the COVID‐19 pandemic.
These were the methods and the results.
This was an open‐label, remote, dose titration trial using daily home self‐monitoring of BP, drug dose, and side effects with linked smartphone app and telemonitoring. Participants aged ≥18 years with uncontrolled hypertension (5–7 day baseline mean ≥135 mm Hg systolic BP or ≥85 mm Hg diastolic BP) received personalized amlodipine dose titration using novel (1, 2, 3, 4, 6, 7, 8, 9 mg) and standard (5 and 10 mg) doses daily over 14 weeks. The primary outcome of the trial was mean change in systolic BP from baseline to end of treatment. A total of 205 participants were enrolled and mean BP fell from 142/87 (systolic BP/diastolic BP) to 131/81 mm Hg (a reduction of 11 (95% CI, 10–12)/7 (95% CI, 6–7) mm Hg, P<0.001). The majority of participants achieved BP control on novel doses (84%); of those participants, 35% were controlled by 1 mg daily. The majority (88%) controlled on novel doses had no peripheral edema. Adherence to BP recording and reported adherence to medication was 84% and 94%, respectively. Patient retention was 96% (196/205). Treatment was well tolerated with no withdrawals from adverse events.
These were the conclusions.
Personalized dose titration with amlodipine was safe, well tolerated, and efficacious in treating primary hypertension. The majority of participants achieved BP control on novel doses, and with personalization of dose there were no trial discontinuations due to drug intolerance. App‐assisted remote clinician dose titration may better balance BP control and adverse effects and help optimize long‐term care.
About Myself
I am a Graduate Control Engineer, who graduated from the University of Liverpool in 1968.
I then worked at ICI in Runcorn for eighteen months, before moving to ICI Plastics Division, because of the untimely death of my father-in-law.
One of my tasks at Welwyn, was to look at control algorithms for chemical plants. For this I often used a PACE 231-R analogue computer.
Note.
- These computers could solve up to a hundred simultaneous differential equations at one time.
- They were programmed by wiring the various amplifiers and potentiometers together to simulate the equations.
- There were only a few transistors in these powerful machines, as all electronics were thermionic valves.
- Two of these machines wired together, were used to calculate the trajectories of the Apollo missions.
They were the unsung heroes of bringing Jim Lovell and Apollo 13 home safely.
Determining Control Algorithms
In a typical problem, I would model the a section of a chemical plant and the control system around it.
This would then lead to recommendations, as to the design and operation of the plant, so that it performed as required.
It could be argued that the body of an animal, is a very complicated integrated chemical plant, with a sophisticated control system.
For instance, if sensors around the body, say you are slightly low on fluids, your brain determines you should have a drink.
Many control loops on a chemical plant are controlled by proportional–integral–derivative controllers, which are commonly known as three-term controllers.
This is the first two paragraphs of the Wikipedia entry for three-term controllers.
A proportional–integral–derivative controller (PID controller or three-term controller) is a control loop mechanism employing feedback that is widely used in industrial control systems and a variety of other applications requiring continuously modulated control. A PID controller continuously calculates an error value
PID systems automatically apply accurate and responsive correction to a control function. An everyday example is the cruise control on a car, where ascending a hill would lower speed if constant engine power were applied. The controller’s PID algorithm restores the measured speed to the desired speed with minimal delay and overshoot by increasing the power output of the engine in a controlled manner.
I wouldn’t be surprised that the app in the smartphone used in the PERSONAL‐CovidBP Trial contained a form of three-term controller.
These are some points about three-term control algorithms.
Changing Of External Factors
One that was the villain in a problem, I dealt with, also affects my body – the weather.
I was asked to look at the problem of a chemical reaction, that overheated in hot weather. But the plant operators solved it by better insulation and ventilation of the plant and the standard three-term controller adjusted itself automatically to the new conditions.
After my stroke, I am on Warfarin for life. I test my own INR with a Roche meter and I have noticed that atmospheric pressure affects my INR. I change my deose accordingly, using a simple algorithm, of my own design.
The More You Test The More Precise The Control
If you take the cruise control example used by Wikipedia, speed is monitored continuously, as I hope, it would be if you were driving yourself.
But obviously, in many systems, where you are using an input with discrete values to control a system, you can’t be as precise as the data you collect.
When my son was dying from pancreatic cancer, he was fitted with a morphine pump, that he could adjust himself to dull the immense pain he was enduring.
- His nerves and his brain ascertained the pain level.
- He then adjusted the morphine level.
- He could get very precise control of his pain, because he was measuring it continuously.
But he was only using simple one-term control (proportional).
Derivative Control Can Be Difficult To Get Right And Can Even Go Unstable
Derivative control is mainly to stop overshoot, but sometimes you will find that it can go unstable, so two-term(proportional+integral) controllers will be used.
How I Control My INR
As I said earlier, I am on Warfarin for life and test my INR with a Roche meter.
The NHS typically tests patients about once every six weeks, which in my opinion as a Control Engineer is too infrequent.
I usually test myself a couple of times a week.
But every so often, I evaluate what daily dose gives me an equilibrium INR level of 2.5.
For the last three years, I have found a dose of 3.75 mg keeps me more or less on 2.5.
- As Warfarin comes in 1, 3, 5 and 10 mg. tablets, I alternate 3.5 and 4 mg.
- Warfarin tablets are easily cut in half using a sharp knife.
- I record INR and dose in a spreadsheet.
I have been doing this now for over ten years.
Is This A Unique Property Of Warfarin?
In this time, I have had five medical procedures, where surgeons were worried, that as I was on Warfarin, I might bleed too much.
For the first, which was to remove a lump from my mouth, the private surgeon wanted to charge extra for an anaesthetist. In the end, I asked what INR he wanted and he said 2.1 should be OK!
- So I reduced the Warfarin level and tested every day.
- I judged it correctly and had an INR of 2.1 on the day of the operation.
- The operation went incredibly well and I went home on public transport.
- The lump turned out to be benign.
- I’ve not had another lump.
After the operation, I increased the Warfarin level and tested every day, until it regained a level of 2.5.
On analysing my doses through the date of the operation, I found that the total amount of Warfarin, I didn’t take to reduce my INR to 2.1, was the same as I took to bring it back up again to 2.5.
Is this a unique property of Warfarin?
Since then I’ve had two cataract operations performed in a private hospital, where the NHS paid. Interestingly, they wouldn’t trust my own INR readings, so I had to get my GP to take the measurement.
I’ve also had gallstones removed by endoscopy at the local Homerton NHS hospital.
- For cases like mine, the hospital hire in a surgeon from the posh Wellington private hospital for one day a week, who brings the specialist tools needed.
- I wrote about this in Goodbye To My Gallstones.
- As it was a more serious procedure, I reduced my INR to a requested 1.0.
Interestingly, I still have my gall bladder, but the surgeon put it on notice to behave.
Conclusion
I would totally agree with the conclusion given in the PERSONAL‐CovidBP Trial.
Personalized dose titration with amlodipine was safe, well tolerated, and efficacious in treating primary hypertension. The majority of participants achieved BP control on novel doses, and with personalization of dose there were no trial discontinuations due to drug intolerance. App‐assisted remote clinician dose titration may better balance BP control and adverse effects and help optimize long‐term care.
I would add some conclusions of my own.
- The app used in the PERSONAL‐CovidBP Trial, seems to have had a good algorithm.
- I suspect the app could also be Internet-based.
These are some general conclusions.
- If you are on Warfarin and have access to a Roche meter, it is possible to lower your INR to the value required by a surgeon for an operation or a procedure.
- Since starting to take Warfarin, I have had four operations or procedures, where others would have had anaesthetic or a sedative.
- In those four operations, I was able to go home on public transport. If I still drove a car, I could have driven home afterwards.
- Private hospitals like to use an anesthetist, as it pumps up the bill.
- Avoiding anaesthesia must save hospitals money.
Well designed apps, based on Control Engineering principles, that help the patient take the best dose of a drug will become more common.
The Weather And My INR
I measure my own INR and adjust my levels of Warfarin accordingly.
I typically take 4 mg of Warfarin one say and 3.5 mg the next, as this average dose of 3.75 mg, seems to keep my INR around the required 2.5.
Recent readings have been as follows.
- 18th December – 2.5
- 21st December – 2.5
- 25th December – 2.7
- 28th December – 1.9
Note.
- I test on Mondays and Thursdays.
- Today’s test was a bit low at 1.9.
- I should also say my left humerus was uncomfortable. Was it because bone was unhappy being in a dry body?
Today I took 5 mg of Warfarin to kick the INR the right way. I shall also test my INR tomorrow, just to be sure.
So why did my IRN drop by an unusual amount between Monday and Thursday?
We have just had storm Gerrit (Who thinks up these names? Donald, Nigel or Vladimir would be better, as they’re Low-life!)
So does the the low pressure suck the water out of my body, thus lowering the INR? And bring pain to my injured arm?
Coeliac Journey Through Covid-19 – A Few Bad Years
A Few Bad Years
In 2007, my wife died of what her consultant at Papworth said was one of the worst cancers he’d ever seen. It was a squamous cell carcinoma of the heart.
Her’s was the only occurrence in the UK that year and someone told me, there were four in the United States.
Our youngest son; George, then died of pancreatic cancer in 2009.
When I had been diagnosed as a coeliac in 1997, my wife and I had told our sons to get themselves tested, as is now advised on the NHS web site.
But George was a sound engineer in the music business, who lived the unhealthy rock-and-roll lifestyle.
A year later, I had a serious stroke in Hong Kong.
I had had a warning a year or so before and Addenbrooke’s recommended I go on Warfarin, but my GP in Suffolk, talked me out of it.
Now twelve years later, my GP and myself manage my Warfarin, where I do the testing of my INR on my own meter from Roche.
But then I am a Graduate Control Engineer!
A couple of doctors have said I have made a remarkable recovery, and I’ll go along with that as the only thing I can’t do, that I could before the stroke is drive, as the stroke damaged my eyesight.
On the other hand, the latest therapy for stroke in the United States is B12 injections and I haven’t missed one of my three-monthly injections since 1997.
If anybody is doing serious research into B12 and stroke recovery, then I would be happy to be a lab-rat.
Are Boots Marching In The Wrong Direction?
My family has used Boots at the Angel since about 1900.
But have they ever been so disorganised?
Yesterday, I went to pick up some Warfarin, which I have taking for a dozen years.
It must be one of the most common and cheapest drugs they dispense.
I needed both 1 mg and 3 mg tablets.
But they didn’t have any 1 mg tablets.
The pharmacist explained that Boots didn’t have any.
Surely, this is a bit like Sainsbury’s running out of baked beans?
Budweiser To Convert Second UK Brewery To Hydrogen
The title of this post, is the same as that of this article on The Engineer.
This is the sub-heading.
Samlesbury Brewery in Lancashire is set to be powered by green hydrogen from 2025, according to new plans announced by owner Budweiser Brewing Group.
This paragraph outlines what will be done at Salmesbury.
The Samlesbury Net Zero project will see the brewery paired with a new hydrogen production facility (HPF), delivered by UK hydrogen services company Protium. Situated adjacent to the brewery, the HPF will provide green hydrogen to meet the thermal demand of the brewing processes, as well as the building’s other heating requirements.
Note.
- A refuelling station for hydrogen-ready HGVs will also be developed as part of the project.
- Heat from the HPF will be recovered and used in Budweiser’s bottling process.
- This is the second project involving Budweiser and Protium, after one at Magor in South Wales.
- Beers produced at the facility include Budweiser, Stella Artois and Corona.
I may have had the odd bottle of Corona in the States, but I’ve generally drunk real ale only since, I started having halves of Adnams with my father at the age of thirteen.
Now, because I’m on Warfarin, I more or less exclusively drink zero-alcohol beers, most of which is Adnams, straight from the brewery.
I’ve yet to find any beer which is less than 0.5 % alcohol, has contained enough gluten to have an effect on my gut.
I have discussed this with experienced brewers and they are not surprised, as the brewing process for zero-alcohol beers doesn’t use much barley.
Conclusion
We need more integrated projects like this, that both decarbonise industrial processes and provide filling stations for hydrogen-powered vehicles.
My First Christmas Snack Supper Of 2022
I saw the first of Marks & Spencer’s gluten-free Turkey Feast Christmas sandwiches in their Finsbury Pavement store today.
Note.
- The only allergens in the sandwich are egg and mustard.
- The cranberry sauce is real, but there appear ti be not enough cranberries to affect my Warfarin-controlled INR.
- Although the Adnams Ghost Ship 0.5 % is labelled as containing gluten, it seems to have no adverse effect on my body.
- I have discussed this with the brewer and they have told me, that there is so little barley in each bottle, that some might find the beer appears to be gluten-free.
I do think it the best humble sandwich, I’ve ever tasted.
Ease Up IPA Goes Gluten Free!
The title of this post, is the same as that of this page on the Adnams web site.
I am now 75 and I have been drinking Adnams beer, almost exclusively since I was thirteen.
My father introduced me to halves of Adnams bitter, whilst playing snooker at Felixstowe Conservative Club.
Part of his logic behind doing this was to teach me to drink alcohol responsibly, like he did and to prevent me ending up like his father, who was a drunk, who died before the age of forty.
The other thing, that my father’s teaching did was give me a preference for good real ale. And especially Adnams!
As I write this, I’m drinking a bottle of their 0.5 % Ghost Ship.
I drink it for three reasons.
- Obviously, I like the taste.
- It is low-alcohol, so it doesn’t affect the action of the Warfarin, that stops me having another stroke.
- I also find, that because the beer is made with low amounts of barley to keep the alcohol low, it doesn’t affect my gut, despite the fact that I’m a coeliac.
I have yet to find a low-alcohol beer, that has had an adverse effect on my body.
But Will Ease Up Be Safe For A Coeliac To Drink?
These paragraphs describe how Ease Up is brewed and the testing of the product.
When producing Ease Up, we now use an enzyme called Clarex® which breaks down gluten-type proteins, reducing gluten content to below 20 parts per million (ppm). Only foods that contain 20ppm or less can be labelled as ‘gluten-free.’ According to Coeliac UK, research shows people diagnosed as coeliac can consume products with gluten present at or less than this level, but customers are advised to consider their own individual tolerances.
Clarex® is added in the fermentation vessel, where it mixes well during a normal, vigorous fermentation. Our beer is tested at the end of fermentation and then, after packaging, it is put on hold while it undergoes a thorough external validation process before it is confirmed gluten free and released. Just look out for the new, updated branding.
Note the phrase about individual tolerances.
Conclusion
It looks like Adnams have produced the ideal real ale to have in your pub, club or house, if you have some coeliac customers, family or friends.
Never did I think, I would ever write about disruptive innovation in the brewing industry.
The Anonymous Widower 