Thursday, 29 June 2017

Atomic Physics in Ancient Greece

Atomic Physics in Ancient Greece

atomic physics in ancient Greece

The first scientific thinking took place 2500 years ago, in ancient Greece.

Mathematics had developed in Babylon at an earlier time and also in Egypt. Records show detailed astronomical recording in Babylon. The great pyramids of Giza were constructed to remarkable mathematical precision. But there no evidence of investigation into the fundamental laws of physics and how the universe functions.

Miletus is the place of the dawn of scientific thinking. It is situated on the west coast of the Kingdom of Lydia, now in Turkey. 






In the 7th century BC Miletus was part of the Persian Empire.

Thales
Thales
Thales (624–546 BC) was a citizen of Lydia and one of the thinkers of Miletus; he is considered to be the first philosopher. His most famous statement is that: 

“We should know more than our parents”.

Anaximander

The most famous pupil of Thales was Anaximander (610–546 BC). He is considered to be the first scientist. He developed the hypothesis of the “apeiron" (ἄπειρον), the primal substance of which everything is formed.

Anazimander
Anaximander thought that the wide variety of substances found in the world must be understood in terms of a single, unitary and simple constituent, which he called the apeiron, the indistinct.

He also suggested that: “The Earth floats in the sky” and that:“The sky continues beneath the Earth”.

Furthermore he proposed that rainwater comes from the evaporation of water from the surface of the Earth. This was a major step forward in understanding the way in which the Earth functions.

He made further suggestions about evolution, recognising that animals and plants evolve and adapt to changes in the environment, and that man must have evolved from other animals. Darwen and Wallace were the next to suggest this, but even now, although evolution is generally accepted, the process leading to humankind is not clear.

Anaximander also proposed the concept of “panspermia”, that life might initially have arrived on Earth from “the heavens”, what today we would call outer space. The idea was presented in the late 20th century by Sir Fred Hoyle and Dr Chandra Wickramasinghe.

The place of Miletus within the Persian Empire made it vulnerable. The years 499–493BC saw the Ionian revolt against Persian rule, the start of the Greco-Persian wars. In revenge, Miletus was destroyed by the Persians.

Miletus and Abdera
The Taking of Miletus is a tragedy written by Phrynincus, and it was performed regularly in Athens in the years following the event.

Leucippus

There was an exodus of the “thinkers” from Miletus to Abdera, on the Aegean coast of Thrace.

Leucippus
One of the exiles was Leucippus, who was born in Miletus in the 5th century and died in Abdera. On his arrival in Abdera, Leucippus founded a scientific and philosophical school, and he wrote The Great Cosmology

Democritus

The most important disciple of Leucippus was Democritus (460–370 BC).

Democritus was born in Abdera. He is regarded as the father of modern science. He apparently wrote many books, all of which have been lost. His ideas predated those of the Enlightenment of the 18th century by more than two thousand years.
Democritus
His most important thought was this: if you were to divide a piece of matter an infinite number of times, what would be left? The logical answer is “nothing”, but as pointed out by Democritus, this cannot be. If you start off with something, you must finish up with something, not nothing. Therefore there must be a point at which matter cannot be further divided.

There is a limit to infinity – there is a finite number of divisions, but a very big number. 

“Any piece of matter is made up of a finite number of discrete pieces which are indivisible, each one having finite size.” (It was Einstein who determined that size)

This led to the concept of the “atom”. “a-” implies a negative, and “tomos” means “cut, slice, divide”. So “atom” meant “cannot be divided, indivisible".

(Tomos bread is sliced bread; tomography, as in CT scan, means digital slicing of the body; tomos, Thomas, indicates twins, divided baby).

From these thoughts Democritus concluded that:

“Just as by combining the letters of the alphabet in different ways we may obtain comedies or tragedies, ridiculous stories or epic poems, so elementary atoms combine to produce the world in its endless variety”.

This is a remarkable vision of the nature of substances and their atomic structure. 

The next remarkable contribution of Democritus was reported by Leucretius. It was based on the rule that “Nothing moves unless pulled or pushed”. Otherwise things remain stationary.

Democritus observed the nature of a sunbeam shining into a deserted and windless room. Within the sunbeam he observed vast numbers of dust particles and puzzled as to why they were in constant movement.

“Observe what happens when sunbeams are admitted into a building and shed light on its shadowy places. You will see a multitude of tiny particles mingling in a multitude of ways in the empty space within the light of the beam, as though contending in everlasting conflict, rushing into battle rank on rank with never a moment’s pause in a rapid sequence of unions and disunions. From this you may picture what it is for the atoms to be perpetually tossed about in the illimitable void.”

“Besides, there is a further reason why you should give your mind to these particles that are seen dancing in a sunbeam: their dancing is an actual indication of underlying movements of matter that are hidden from our sight. There you will see many particles under the impact of invisible blows, changing their course and driven back upon their tracks, this way and that, in all directions. You must understand that they all derive this restlessness from the atoms. It originates with the atoms, which move of themselves. Then those small compound bodies that are least removed from the impetus of the atoms are set in motion by the impact of their invisible blows and in turn cannon against slightly larger bodies. So the movement mounts up from the atoms and gradually emerges to the level of our senses, so that those bodies are in motion that we see in sunbeams, moved by blows that remain invisible.”

Democritus thus suggests that the dust particles move perpetually because of impact by the atoms of the air.

The same process can be observed form the “spontaneous” movement of pollen grains on the surface of water. The next person to suggest that this is the result of collisions by atoms was Albert Einstein, 2500 years later. Einstein used his observations to calculate the size of atoms.

Democritus was an avid observer of nature, observation being the true basis of logic. He stated: “To a wise man, the whole earth is open, because the true country of a virtuous soul is the entire universe.”

Socrates and Plato

Socrates (470/469–399 BC) was rather more utilitarian. Most of his thoughts were reported by Plato (428/427 or 424/423 – 438/437 BC).

Socrates
Plato
 Plato’s Phaedo describes the last days of Socrates and his death by poisoning with hemlock. He quotes Socrates:

“I had expected to be first told that the Earth was flat or round, but also that, afterwards, the reason for the necessity of this shape would be explained to me, starting from the principle of the best, proving to me that the best thing for the Earth is to have this shape.”

“If the Earth is at the centre of the world, then show me how being at the centre is of benefit to the Earth.”

Plato also mentions a further comment of Socrates:

"When ‘physicists’ had explained that the Earth was round, he rebelled because he wanted to know what ‘good’ it was for the Earth to be round; how its roundness would benefit it.”

Zeno (c450 BC)



Zeno was an important philosopher, but little is known about him. He lived in Elea, a town of Greater Greece (Magna Graecia ), now Viela in the Cilento region of southern Italy. 


Elea today

Zeno is famous for "Zeno's Paradox". 

It is similar to the assertion of Democritus concerning the absurdity of the infinite divisibility of matter, and that there must be a finite but very small ultimate and indivisible "atom".

Zeno took the same approach to length and distance: could there be a length that is infinitely small? To discuss this he used the analogy of a race between Achilles and a tortoise. The tortoise was given a 10 metre starting advantage, and the challenge was for Achilles to catch up with the tortoise. The logical argument is that Achilles would never catch up.



The logic went like this: by the time that Achilles covered the ten metres to where the tortoise started, the tortoise would have moved forward a few centimetres. By the time that Achilles have caught up these few centimetres, the tortoise would have moved forward a few more centimetres. By the time that Achilles have caught up these very few centimetres, the tortoise would have moved forward a very few more centimetres. And so it goes on ad infinitum

Achilles would therefore, by logical thought, never catch up with the tortoise, but Zeno recognised the absurdity of this and felt that an infinitely small distance cannot exist, it would no distance. Multiple divisions of length cannot result in no distance. There must be a finite minimum distance.

It was more than 2,000 years later that Max Planck calculated the shortest distance possible, the Planck Length (also known as the Bronšten Length). It is approximately one millionth of a billionth of a billionth of a billionth of a centimetre, 10-33 centimetres. It is very small but finite, a measure of the quantum granularity of space time.

Epicurus
Epicurus
Epicurus (341–270 BC) was a pupil of Democritus. His assertion was “Knowledge in place of ancient myths and religion”. This continues objectivity through careful observation.

Lucretius
Titus Lucretius Carus
Lucretius (99–55 BC) was an influential follower of Epicurus. 

“Religion is ignorance; reason is the torch that brings light.”

“Nature is clamouring for two things only, a body free from pain, a mind released from worry and fear for the enjoyment of pleasurable sensations.”

Lucretius wrote a manuscript De Rera Natura (On the Nature of Things) for the benefit of the Romans, to whom he hoped to bring Epicurean enlightenment.

His greatest personal contribution of natural philosophy within this manuscript is contained in the remarkable and profound quotation:

“It must not be claimed that anyone can sense time by itself apart from the movement of things”

Time is only relative. Without movement there is no time. This also predated Einstein, who re-introduced the assertion that there is no absolute time. It is fundamental to his Special Theory of  Relativity. 

But the assertion of Lucretius that “religion is ignorance” brought him no friends in Rome, and his attempt to bring enlightenment to the Romans was a failure. After the Christianisation of the Roman Empire things became worse. Even as late as the time of the Renaissance the Roman Catholic Church attempted to suppress the words of Lucretius. In the Florentine Synod of December 1516 it prohibited the reading of Lucretius in schools, and in 1551, the Council of Trent banned his work.

Pythagoras

Pythagoras
Pythagoras (570–495 BC), like Epicurus was born on the island of Samos. His contribution was in the field of mathematics, at that time not obviously related to atomic physics. However now we know the connection between the two: the famous equations of Maxwell and Einstein laid the foundations of 20th century and present day physics.
Einstein equation
We now appreciate that the intuition of Pythagoras was correct: mathematics allows the world to be described and the future to be predicted (for example the occurrence of an eclipse of the sun).

The understanding of atomic physics by the thinkers in Ancient Greece was truly remarkable. They envisaged the atomic structure of matter, the concept of a minimum length or distance, that time is not a constant in the universe, and that laws of physics have a mathematical basis. 

Much of their understanding has probably been lost in the destruction of their written records.

Friday, 23 June 2017

Unexpected benefit of statins after heart attack (MI)




Hokusai - Fuji

There is no value in knowing your blood level of cholesterol.

If you do not have any evidence of heart disease, you do not need to take a statin.

The small benefit of statins is nothing to do with the fact that statins reduce blood levels of cholesterol.

If someone who is supposed to be taking a statin does not experience a reduction of the blood level of cholesterol, then he or she is not taking the tablets.

But:

Statin medications can be helpful if you have heart disease.

…………………..............................................................

There is no value in knowing your blood level of cholesterol.
I have previously drawn attention to the fact that the blood cholesterol level is not overall a useful predictor of life expectancy, risk of myocardial infarction (MI, heart attack) or other manifestation of coronary heart disease (CHD). 

The most important long-term study of the influence of the blood level of cholesterol was undertaken in the town of Framingham, Massachusetts, USA. It was a thirty year study, and it will never be repeated as to do so would be both pointless and prohibitively expensive. The conclusion was as in Figure 1.


Figure 1: Conclusion from Framingham

In the Framingham study, there was in young men a relationship between blood cholesterol and survival, but in this age-group the risk of CHD is now extremely low. The Framingham study was of people up to the age of 65 years at the time of recruitment. However, after the age of 70 years a high cholesterol appears to give a very significant survival advantage. This could not have been recognised in the Framingham study, but the great majority of CHD deaths occur in this age-group.

If you do not have any evidence of heart disease, you do not need to take a statin.
The chance of a middle-aged man with no known heart disease benefiting from long-term statin medication taken for five years is now less than 0.1%, one in one thousand. The chance of experiencing unwanted but significant muscle pains might be about 1% (incidence very much disputed), meaning that untoward effects would be 10 times the chance of benefit. In women the chance of benefit is much lower, but the risk of untoward effects is the same.

In the absence of heart disease, statins need not not be taken and are more likely to do harm than do good. So-called “primary prevention” should stop. There would have been a benefit in high risk men in about 1970 (although statins would not be available for another 20 years), but not now that the epidemic is at an end.

The benefit of statins is nothing to do with the fact that statins reduce blood levels of cholesterol.
There is great concern that the data from the statin trials is not generally available. Despite many requests or demands, the data is deliberately with-held from public scrutiny. The data can be seen by only the close and self-appointed Cholesterol Treatment Trialist Collaboration. This is a cover-up, and what is being covered up in particular is the lack of relationship between cholesterol-lowering and benefit, most importantly reduced death rate). 

However, such data was made available from the first statin primary prevention trial, WOSCOPS, the West of Scotland study, a trial of pravastatin in men with high cholesterol but no history of heart disease. The second WOSCOPS paper showed clearly that there was no relationship between cholesterol lowering and subsequent mortality. This is shown in Figure 2. 
statins not related to cholesterol
Figure 2: lack of relation between cholesterol-lowering and heart event rate

One group did not show any reduction of the blood level of cholesterol and it was assumed that the subjects did not take the statins provided. There are four groups defined by the reduction of cholesterol levels (by 12, 24, 31, 39 percent). 

What was expected was that the CHD mortality and event rate would go down 
corresponding to the percentage reduction in cholesterol (total or LDL). This did
not happen.


Despite the wide variation of cholesterol-lowering, we can see in Figure 2 that within these four groups there is no significant difference in the cardiac event rates, including mortality. In the conclusion of the paper the authors state:


Figure 3. Conclusion of WOSCOPS trial

The authors are correct, as becomes clear nearly thirty years after the trial was published. The small benefit of statins in respect of CHD is not due to lowering of cholesterol, but is the result of an independent and at the time of WOSCOPS (published in 1995) an unknown function of statin medications. 

If someone supposed to be taking a statin does not experience a reduction of the blood level of cholesterol,then he or she is not taking the tablets.
In the WOSCOPS trial there was a group of subjects in the active treatment randomised half in whom there was no change in the blood level of cholesterol. They had a higher event rate than the other groups and similar to controls. The authors concluded that they had not been taking the pravastatin that was prescribed.

Statin medications can be helpful – if you have heart disease.
There is no doubt that statin medications do give benefit, albeit very small. Soon after the height of the epidemic in 1970–1980, there was a reduction of deaths in those who received statins, in WOSCOPS from 4% deaths at five years in controls to 3% in those treated. This means that just one man in 100 without a history of CHD who took (prava)statin for five years did not die. 

Yes, there was a benefit and it was also shown in subsequent trials. This was the time when the death rate from CHD was very high. Now that the epidemic is close to the end, the CHD death rate and therefore risk to the population has dropped by a factor of about 20. The benefit of  statins to the general population has also fallen and so fewer than one in man in 1000 will now benefit. 

The beneficial effect of statins can now be understood, but only by those with open minds, sadly very few.

Unexpected: the effect of statins immediately after myocardial infarction

It is immediately following myocardial infarction (MI) that statins are most effective. This has been demonstrated in an important observational study from Frankfurt, Germany, and it has barely been acknowledged.

Follow-up of immediate survivors of MI fell into three groups: 

* those previously receiving statin therapy and it was continued following admission to hospital (369); 

* those receiving statin therapy and it was stopped on admission (86); 

* those not receiving statins and who were not prescribed statins (1151).

There were major differences in the outcome during the subsequent 30 days, differences in death rate and repeat MI. These are shown in Figure 4.

statins valuable immediately after heart attack
Figure 4. Statin and event rate after MI – no statin, statin continued, statin stopped.
Look at this important graph carefully. There were immediate differences, shown clearly at just two days after MI. At this early stage the major event rate in those who did not take statins was 1.6% (blue), but in those taking statins much lower at 0.6% (green). However in those who stopped taking statins on admission hospital had very much higher early event rate at 4.7% (brown).

The 30-day event rate shows the same pattern. In those who did not receive statins (blue), the mortality or major second MI rate was 7.5% at 30 days. The outcome was better in those taking statin before and after admission, with 30 day mortality or second MI rate of 3.7% (green).

But the other group was most interesting, those in whom statins had been taken before admission but stopped on admission with MI (brown). The 30 day mortality and major event rate was highest of all in this group, 14%.

There is clearly a very early effect of statins, but also a rebound effect: stopping statin medication leads to a higher death or repeat MI rate than if statins had never been taken.

The immediate advantage of statin following MI, and the serious rebound effect, indicate an immediate effect of statins, something other than the long-term cholesterol-lowering effect. This should be very interesting, but I have seen no signs of interest.

It is likely that this effect is anti-inflammatory. The acute MI is the result of an intense inflammatory process as the atheromatous plaque within the coronary artery becomes unstable and ulcerates, “like a boil” (Uffe Ravnskov), with superimposed fresh blood clot completing the occlusion of the artery. Under these circumstances an immediate anti-inflammatory medication would be very valuable, and we see this with the emergency use of aspirin. 

The anti-inflammatory statin would have held back the inflammatory process, and its sudden cessation can be expected to result in a equally sudden enhancement of this inflammatory process with serious and sometimes fatal consequences.

It must be emphasised that statins do have some clinical benefit, but this is nothing to do with their ability to reduce the blood level of cholesterol. If statins are to be given on account of heart disease, then the decision should be based on clinical criteria and not on the basis of the blood level of cholesterol.

A new finding

There is something else new concerning statins benefiting patients with heart disease. This was presented at the European Heart Society meeting in Prague in May 2017. The lead author was Dr Nay Aung from Queen Mary University of London.

The observations were that people taking statins had a thinner left ventricular heart wall compared to controls. A thick heart wall is a bad thing - left ventricular hypertrophy, that can lead to heart failure. 

Dr Aung commented in his press release: “Statins have other beneficial, non-cholesterol lowering, effects. They can improve the function of the blood vessels, reduce inflammation, and stabilise fatty plaques in the blood vessels." He then demonstrates that statins can have a beneficial action on the structure and function of the heart.

Forget the absurd diet-cholesterol- heart hypothesis. Statins are intriguing in their effects, but these are not publicised or investigated in detail.

The pharmaceutical companies are very happy with the vast prescribing to normal people of statins to lower cholesterol – in itself, pointless.





Thursday, 25 May 2017

The importance of the sun - more experience from Lancashire UK


The Sun and Coronary Heart Disease (CHD) - evidence from Lancashire

Sometimes important evidence can be found very close to home.


Figure 1: Blackpool, on the coast of Lancashire

Previous Posts have shown the epidemic nature of deaths from coronary heart disease (CHD) during the 20th century. The epidemic emerged in the mid-1920s, and this is very clearly recorded in the UK and in the USA. As it occurred simultaneously in all continents of the world (with the exception of the tropics) it can be regarded as a pandemic. The death rate increased rapidly to a peak in about 1970 and it became the major cause of death for several decades in many countries. Following the peak the death rate went underwent a rapid, unexpected, and spontaneous decline

The cause of CHD

The cause of CHD is not clear. Although there has been a ready acceptance that it has been due to faulty diet, research (usually ignored) has shown that this is not the case. I have suggested that a microbiological cause is the most likely, the only one that fits the evidence and our understanding of medical science.

But the incidence of CHD has varied; there are in particular social and geographical variations. These might not tell us directly the cause of the disease, but they might indicate a variation of susceptibility, and this will help us to understand the condition.

The Sun

The sun is related to the incidence of CHD. The sun appears to be protective, and conversely the incidence of death from CHD is highest among people with little exposure to the sun. This is demonstrated in a number of studies.
  • People with CHD have on average lower blood levels of vitamin D than matched controls. The blood level of vitamin D is an index of exposure to the sun.

  • We have seen in previous Posts that the death rates from CHD in the UK are closely linked to latitude. The further north the town of residence, the higher the overall adjusted death rate from CHD. However there is no difference in dietary patterns or any other personal external risk factor.
There is more evidence from my place of residence in Lancashire that indicates a protective effect from the sun. 

Figure 2: Location of south Lancashire

4 towns in Lancashire


Figure 2: South Lancashire – Blackpool, Preston, Blackburn, Burnley
 (the blue spot is where I live)

Let us consider four towns in Lancashire, UK : Blackpool, Preston, Blackburn, and Burnley. They have had different death rates from coronary heart disease (CHD), and the data shown in Figure 3 are from 1980. The death rates now are very much lower as the epidemic approaching its end.


Figure 3: Annual death rates from CHD, per 100,000 population, 1980 

What is the reason for this? The populations are very similar, all having a relative degree of socio-economic disadvantage. There is no suspicion of dietary difference, although in general diet appears to be of little or no importance in consideration of CHD death rates.  The maximum elevation is Burnley at 105 metres above sea level. The four towns lie on the same latitude, 53.8 degrees north of the equator. Blackpool is on the coast and it has been the traditional holiday destination for the populations of the three industrial times. 

Could differential exposure to the sun be the solution to the varying CHD death rates of the four towns? The answer is “Yes”.

The sun in Lancashire

The annual sunshine data is available from the UK Met Office, and the results are as follows:

Figure 4: Average annual hours of sunshine
The reason for the sunshine variation is based on the location of the coast of Lancashire on the Irish Sea, with a prevailing wind off the sea. It is fed by the Gulf Stream, and so the sea is relatively warm (considering its latitude) and the air immediately above the sea is moist. At an altitude of only 500 metres the air is cool, in keeping with the proximity to the Arctic. As the air from the coast reaches the hills close to Blackburn and Burnley (particularly Pendle Hill (557m, 1827 ft) cloud forms and sunshine is reduced.

Figure 5.Cloud over Lancashire, looking north from my house
The photograph is looking north, on a day that Blackpool, on the coast, left of the image, would have a clear blue sky, as in Figure 1. It can be seen that the hills generate cloud cover that reduces sun exposure of the populations of Blackburn and Burnley.

If we plot CHD death rates against hours of sunshine we find an excellent data fit: the greater the annual sunshine received by the four towns, the lower is the mortality rate from CHD.

Figure 6: Regression of CHD mortality and annual hours of sunshine
Once again we see the same pattern: increasing exposure to the sun appears to give some protection against CHD death. We see this not just in these four Lancashire towns, but also three other Lancashire towns at different altitudes; in cities at different altitudes in the USA; in towns at various latitudes within England and within the UK generally; in cities at various latitudes within France, and within Europe overall.

Protection by the sun

I have previously indicated that CHD has been a 20th century pandemic occurring in all continents simultaneously, with the exception of the tropics. It arose in the 1920s, reached a peak in about 1970, and thereafter underwent a dramatic and  spontaneous decline by the end of the 20th century. The only realistic explanation is that it has been due to a micro-organism, the precise identification of which is not clear.


Figure 7: The epidemic of CHD in the UK

The protection given to certain populations by the sun is therefore likely to be mediated by maximal immunological competence. It is known that the sun has this effect, demonstrated in its well-established relationship to tuberculosis. Also it is known that damage to immune mechanisms will increase susceptibility to CHD. There is also laboratory evidence of the immune / inflammatory cascade being enhanced by vitamin D through vitamin D receptors. More of this will follow in subsequent Blog Posts.

The sun has many benefits. Bone health is well-known. Immune competence is not so well known but it is of great importance.



Latitudes, degrees north of the equator
Burnley 53.7893
Blackburn 53.7486
Preston 53.7632
Blackpool 53.8175