Sunday, 15 October 2017

Brexit Negotiations

    I find stressful, and begin to resent, the shilly-shallying on the Brexit negotiations.   
    Here is a simplifying suggestion.  Britain has offered to honour commitments made during membership.  Barnier wants to know how much that is.  Why not everything that we were paying before the brexit referendum? But during the transition period, we receive all the benefits that we received as a full member before the referendum. (No more closed-door stuff.)
    At least we know how much that was, and that we can afford it; and we know that it is regarded as value for money by 48% of Britons.  
    During the transition period we enter no new commitments, and we pull out, one by one, from the costs and the privileges of membership. The transition ends when the negotiations end. They might take decades.
    Yours sincerely, Ian West
--
Ian West, 9 Thenford road, Middleton Cheney, Banbury, OX17 2NB. (Tel: 01295 713889; mob: 07906 750986)

Friday, 13 October 2017

“Coppola Comment” Comment

“Coppola Comment” Comment

Frances Coppola is always an enjoyable read, enunciating good sense in lucid prose. But she can be teasing, as in her latest blog.

Growth:

     Like organisms, I believe economies can grow until they approach maturity, when they will enter a ‘steady-state’. It is neither possible nor desirable to grow for ever. By the way, GDP cannot be used as a measure of growth unless corrected for devaluation. True growth (in wealth) would have to involve either an increase in population or productivity (per worker), or both.  I cannot see why anyone should want a mature economy to grow.  No sane Briton could want an increase in the population (of Britain), nor an increase in the ratio of concrete to green-space, in Britain.  There will (in Britain) be even less interest in the growth of economies elsewhere in the world. 

Inflation:

     I suppose inflation is (in essence) the willingness of some people (sufficient people) inside a currency zone to pay more for a standard item (or sufficient basket of items).  And I suppose this could happen if the items become more scarce, or if the currency becomes more plentiful. 
     I assume that the conventional aim of 2% inflation depends entirely on politics and psychology; not on economics. People are unwilling to accept a lowering of money wages. If government wishes to lower real wages (for whatever reason), that can be achieved most easily by fixing money wages and waiting for inflation (devaluation). In Japan, with a mature and stable economy, I cannot see why anyone could possibly want inflation, whether in the form of devaluation, or of growth.  (If Japan wanted inflation, I think that could be achieved, with a printing press.) 

Interest Rates:

     From Cowen, I read “Peter Olson and David Wessel write:
‘The natural rate of interest, also called the long-run equilibrium interest rate or neutral real rate, is the rate that would keep the economy operating at full employment and stable inflation’.”  When base interest rate was the only lever the Central Bank could pull, the Olson and Wessel definition probably made some sense; the central bankers spent their time sliding the lever up and down while watching their two indicators of success. Quantitive easing provides another lever for the Central Bank, and doubtless upsets the theory of ‘natural interest rate’.  Even without the complication of quantitative easing, it seems quite possible that the concept of Natural Interest Rate contains internal contradictions: [a] Full employment may not be ‘natural’. [b] Full employment, when achieved, might not be compatible with the interest rate required for stable inflation (unless stable inflation is used to provide a definition of “full employment”).

Coppola clearly knows all that, and in her blog is not so much dismayed, as laughing at the discomfort of the economists who were armed not with basic principles but with rules of thumb.  

Tuesday, 10 October 2017

Angina – Some Questions

Angina — Some Questions

     The heart must deliver oxygenated blood to (inter alia) the brain, skeletal muscle and the heart muscle itself. Exercise increases the oxygen requirement of the skeletal muscles, and the heart pumps harder. That increased effort, in its turn, increases the oxygen requirement of the heart muscle. The consensus view is that ‘diseased’ (or atherosclerotic) arteries, partly occluded with cholesterol-rich plaques, require raised blood pressure, so more effort is required from the heart. If the coronary arteries supplying the heart muscle are healthy, blood pressure would rise, and in time ventricular hypertrophy would be evident. But if they are themselves diseased (>69% occluded), the heart muscle becomes inadequately oxygenated when under this increased work load; this ischaemia causes pain — in the myocardium (and referred areas). This predictable, effort-related, chest pain is called stable angina. (A very similar pain can be caused by emotional stress, where the transient cardiac ischaemia is presumably the result of vaso-constriction caused by adrenaline and the ’stress-response’; a significantly different mechanism.)

Cause of Pain
     Note that ischaemia in the brain causes fainting, but not pain. Ischaemia in the legs might be expected to cause pain there, or at the very least weakness but, by some mechanism, the legs keep working and it is the heart muscle (which also keeps working) that experiences pain. The biochemistry causing the pain is still mysterious but may involve adenosine, and possibly ATP [1]. 

Cause of Sclerosis
     If you ask what ‘causes’ the atherosclerotic obstruction the answer given is indistinct. The literature will tell you that the major (modifiable) risk factors for cardiovascular disease are [2]:
  • Blood Cholesterol (LDLch > 3, HDL< 1.0 for men; mmol/L).
  • High fasting Triglyceride:HDL ratio (>2:1)
  • High Blood Pressure (> 140/90 mmHg).
  • Diabetes [or Impaired Glucose Tolerance] (fasting blood glucose >7mM [>6mM]; HbA1c >48 mM [>42 mM])
  • Smoking
  • Obesity (Waist:Hip > 0.9 for men)
  • Inactivity 
  • Excess alcohol
  • Mental (emotional) Stress.
     But Risk Factors do not in general cause anything; they merely correlate, they are markers. Amongst them there may be one 'cause' that causes all the rest. Or the 'causemay still elude detection. It is said that these risk factors interact, either additively, or possibly even synergistically [3]. But they are clearly linked. For example, it is easy to see that narrowed arteries might necessitate raised blood pressure; but it is harder to see how raised blood pressure could directly cause narrowing of arteries; bloating rather. 
     It is hard to see from this list what mechanism really ‘causes’ atherosclerosis. There are two theories; one is called the “reverse cholesterol transport’” hypothesis, the second theory involves lipid oxidation.
     Evidence for the Reverse Cholesterol Transport hypothesis [3] comes from finding that unloaded HDL apoproteins, capable of binding cholesterol, is protective. So also is contriving (by gene-therapy) to raise circulating levels of various of the protein components of HDL such as apoE and apoA [5].
     The Oxidised Lipids hypothesis [4] notes that the oxidation of phospholipids bound in the LDL particle, and especially phospholipids containing arachidonic acid, are inflammatory. In the presence of such oxidized LDL, HDL is found to be anti-inflammatory. What starts the inflammation is not clear, but an early step is entry of monocytes from the blood into the artery wall [5], possibly recruited by oxidised LDL, or by Cholesterol peroxides, which are particularly inflammatory.. The monocytes then become macrophages and generate cytokines from arachidonic acid.  Apolipoprotein B in LDL becomes tagged with a product of lipid oxidation, and is then accumulated by cells in the artery wall. Lipoxygenase-negative mice have “significantly” less atherosclerosis. (Hmm!). However, in humans, vitamin E and other antioxidants have proved clinically ineffective in combating atherogenesis. It seems that the growing plaque can do one of three things: [a] regress, [b]  stabilise, [c] rupture. Even the ruptured plaque can stabilize, but leaving the artery with a restricted lumen [5]. 
     Accounts emphasise different aspects but none are clear on the first step. Does dietary cholesterol get oxidised by oxygen radicals generated in the intimal layer of the artery wall? Nor is it clear why the body generates all this fuss; is the inflammation and the plaque protective?
     Isoprostanes (peroxidized products of arachidonic acid and other polyunsaturated fatty acids that participate in the perception of pain) flag the presence of oxidative stress. They are found in the urine, particularly of smokers. So, smoking correlates with increased oxidative stress, perhaps by blocking the flow of electrons to oxygen, for smoke contains both CO and CN-. 

     Is there a feedback loop here? with the ischaemia causing radicals, which then attack the intima and cause further occlusion? 

REFERENCES:
[1]  Belardinelli & Pelleg ( 2012) Adenosine and Adenine Nucleotides: From Molecular Biology to Integrative ...edited by Luiz Belardinelli, & A. Pelleg
[2]  http://www.mayoclinic.org/diseases-conditions/angina/basics/risk-factors/CON-20031194
[3]  Reverse transport review – https://www.jci.org/articles/view/11538; 
[4]  Navab et al. (2004) The Journal of Lipid Research, 45, 993-1007.
[5]  Oka, (2005) Acta Biochim Pol. 2005; 52(2): 311–319. 

See also: 
Temel, RE & Brown, JM (2015) trends Pharm. Sci. 36, 440–451, July 2015
https://www.healio.com/cardiology/learn-the-heart/cardiology-review/topic-reviews/coronary-artery-disease-stable-angina 
The Joint British Societies third consensus report (JBS3) is published at http://heart.bmj.com/content/100/Suppl_2/ii1
Leach (chatty review) Br J Pain. 2013 Feb; 7(1): 23–30.




Friday, 15 September 2017

The ‘Signed for’ Scam

The ‘Signed for’ Scam

Have you received unsolicited anonymous mail containing — Nothing?

     I recently received a small yellow padded envelope by second class ‘Royal Mail Signed ForTM’ delivery. I was out when it was first delivered and I had the choice of going down to the sorting office in the town some miles away, or requesting that the package be re-delivered on  the next available day. I chose the latter as the least inconvenient; I had only to stay in the house till the package arrived. 

     It was addressed to “The Manager”, but I signed my usual squiggle on the little electronic box the postie held out for me. Inside there was nothing. Figuring that the operation would cost the sender over £1 (including envelope and franking), I began to wonder what the purpose was. I went online to search for similar experiences. 

     One blogger posted the suggestion that the hidden reason was harmless enough, simply that of inflating apparent turnover of online sales to impress clients or competitors. Well, I saluted the ingenuity of both the poster and the blogger, for I had not come up with any cogent explanation of my own (not that I had tried that hard).

     Then I came across the suggestion that the scam is more sinister and works as follows. An innocent online customer buys and pays for an item and is given the ‘tracking number’ (in this case KK461028710GB). The scammer posts an empty package to an arbitrary addressee who innocently signs for the package before opening it and finding it empty. The ‘mark’, waiting in vain for his item, eventually checks with Royal Mail who tell him (to his surprise) that the item has been delivered and shows the irrelevant signature. No redress!  

     The scammer no doubt trusts that the innocent addressee, as he is little affected, will forget the incident. In order to frustrate that expectation I post this here and invite comments. 

Sunday, 10 September 2017

Yanis, and DiEM25

Dear Yanis, and DiEM25,

     A year and a half ago, the launching of DiEM filled me with hope, particularly in the context of the British referendum. Since then DiEM25 seems to have slipped off the main stage, which is a pity. I wish I could help it re-find its momentum.
    One way of seeing the problem is when we hear Yanis Varoufakis describe his confrontations with the central powers of the EU. They met, talked, listened. He left. They did nothing. My first analysis was that they did not understand. Indeed, I found it very hard to repeat the argument to myself;  about how it is all Germany's fault, so stubbornly bent on recycling money so that the Greeks can go on buying Mercedes cars. My second analysis is that Yanis does not understand. Oh yes, he understands the  economics; but the crux, the movable fulcrum, the point in the argument against which a popular movement might push and win — has he identified that? 
    Martin West thinks the single currency is a mistake. No single interest rate can suit both Germany and Greece. Put another way: how does it work in the USA, and how can Ecuador and the USA both use the same currency?  I believe there is an understanding in the USA that federal money must be returned to poor states if they are going to be kept in the union. I do not know how. There may, in that complex and subtle constitution, be a degree of political integration that is still missing in Europe. Or is it just the common language? But perhaps we do agree that something needs to be done about the Euro Currency Union.  
     Yanis Varoufakis suggests there is a democratic deficit? Before the Brexit Referendum, that sounded like a promising slogan, but we now see what a mess is made if complex issues are decided by simple people. It is not obvious to me that it is democracy that we lack. I believe it is education.  
     Can Europe be 'cured' by allowing more power to the EU parliament?  I doubt it. Or by curbing the EU civil service? Possibly. But we have to recognize that the origin of the EU depended on the dreams of a very few people; integrated Europe is not the product of a popular dream. Only by imbedding the guiding force in a hidden and inaccessible committee was it possible to get the project of a united and inter-dependent Europe off the ground.  It is true that we pay lip service to democracy, but I doubt we really believe in it, except to rally forces against flagrant corruption. I do not think we are quite there yet; I mean the corruption is not flagrant enough; people are not convinced that revolution would improve their situation. 
     I think the Pro-Europe lobby finds its greatest traction at present by showing that the EU is protecting workers rights, clean beaches, fish-stocks and, by instituting uniform production standards, is allowing economies of scale. These are the tangible and practical benefits of integration. For me, and for a considerable fraction of Europeans, there is some appeal in the thought that United Europe could be (would be) a great power. Britain being part of Europe would allow Britain to effect some control in world affairs.
     Arguably the most depressing sign at present is the resurgence of nationalism. The British seem to think they are special (which may be true), but special in a ‘good’ way; this, to any travelled person is clearly a delusion. 
     Yanis Varoufakis believes that right-minded people will spontaneously support socialism. In Britain, they do not; or they are too few. He suggested that all businesses subvert a fraction of their profits towards the public purse, to illustrate the principle that wealth is generated by a combination of capital and labour**. That suggestion sounds drastic and risky, and unlikely to garner mass public support. (Though admittedly, it is little different from our widely accepted but as widely resented corporation tax.) 
    But thank you DiEM25; please keep the ideas coming.
    Yours sincerely, Ian West

Friday, 25 August 2017

Cholesterol and Statins

(First posted on 2014/02/27 by ianwest2; reposted 2017/08/25)

A year or two ago (Feb, 2014) I heard Professor Ian Young, (Director of the Centre for Public Health, Queen’s University Belfast) give the Albert Latner lecture at Newcastle University on “My cholesterol — why is it so high?”. It was a most frustrating affair. Why?
The man presented no chink of doubt, he missed some serious points, and he spoke like a missionary, or a man whose salary is largely augmented by the manufacturers of statins. We must all take statins from infancy up (we were told). He kept saying that a 1mM(*)  drop in total cholesterol causes a 25% lowering of risk of vascular event; but, while his curves showed a steep line of correlation for 40 year olds, it was an almost flat line for 80 years. (So for me there is practically no benefit).

But a more important point: In no case was the vertical axis on any of his graphs ‘General health’; he was only talking about ‘Rate (or risk) of vascular event’. It has been said that "to a hammer, everything looks like a nail", and to a cardiologist the only objective is to lower the risk of a ‘vascular event’. What about the adverse side-effects; the muscle pains, and increased risk of diabetes (both of which Young conceded), Alzheimer’s, ALS, and Parkinson’s (which were mentioned by Stephanie Seneff; https://people.csail.mit.edu/seneff/)?

Cholesterol is essential. Ian Young correctly remarked that blocking the synthetic pathway at HMGCoA synthase (which is what statins do), will indeed cause a shortage of cholesterol and lead to scavenging pathways and the relocation of existing cholesterol. If the scavenged cholesterol is from coronary plaques, well-and-good; but what if it is scavenged from brain myelin or muscle cell membranes (as emphasised by Stephanie Seneff)? And what about ubiquinone and dolicol, which are also essential and also on the pathway blocked by statins (as emphasised by Stephanie Seneff )? If there ARE INDEED adverse side effects of statins, it is easy to see why!

So the clinical debate should be about the side effects versus benefits. I heard a paper in a Glasgow Heart meeting in the late 1990s which concluded that for over 40 year olds (or was it over 50?) the OVERALL benefits of statins do not outweigh the OVERALL damage. I was impressed (staggered, indeed) at the failure of the clinical cardiologists to see that thisif true—trumped the undenied fact that statins lower cardiovascular risk.

In 2014, aged 72 but in perfect health, I concluded I was certainly not going to take statins. I did not feel I needed them. And whether or not I should lower blood cholesterol there is something too utterly daft about poisoning myself at great expense in order to achieve that; and simply to switch from a healthy death from a coronary to a lingering death from mental, muscular and neurological decay. If I were under 40 and had familial hypercholesterolaemia (**), I think I would try diet, red-wine, and niacin (e.g. brewer’s yeast) before I tried statins.   

Professor Ian Young talked away about nuts, expensive margarine, salt, exercise, the ‘J’-curve for alcohol, etc. But he conceded that only 10% of our cholesterol comes from diet. So, surely the question is why do we MAKE too much? What regulates the synthetic pathway? [***] Does alcohol in excess of 2 units per day, or smoking, etc, up-regulate the synthetic pathway, or affect the partitioning between pools of cholesterol, e.g. by enhancing oxidative damage? What is the rôle of lipid oxidation (briefly mentioned by Young)?

Young pointed out that HDL-cholesterol is “good”; that low ‘cardiovascular risk’ correlates with higher HDL (in the 1 – 2 mM range, independently of LDL or total Ch.); in fact high HDL-Ch is 10-fold healthier than low HDL-Ch (while low LDL-Ch is only 3 times healthier than high LDL-Ch); the best predictor of heart disease is therefore the ratio LDL/HDL, the next best is HDL, the least good is LDL or total blood cholesterol. So, further good questions would be: what determines partitioning of cholesterol between the various ‘pools’ of cholesterol (HDL, LDL, cell membranes and atherosclerotic plaque, its locus operandi (where it is needed, in muscle and nerve membranes), and its locus morbidus (i.e. coronary plaques where it appears to be deleterious)?  Also, what is the rôle of lipid oxidation in affecting the partitioning? Presumably the HDL particle is picking up and re-locating cholesterol and is wholly good. But it is 'HDL-cholesterol' that is measured, so we do not know if the HDL is largely unloaded or nearly full; the latter giving the impression of plenty of HDL particles, but actually being nearly useless as a scavenger. There is a route for elimination of lipid, lipid-cholesterol-ester and cholesterol which involves liver, bile and gut. Guessing here, and maybe naively, but is it damaged (e.g. oxidized) fat/cholesterol that is eliminated, rather than merely surplus? So, there are plenty of unanswered questions.

Perhaps the coronary plaques are, in a wider sense, beneficial. After all, they protect us against suffering from Alzheimer’s disease, and a lingering death! What, in any case, are the evolutionary benefits (to the genes) of surviving beyond the age of 70? The benefits must be very small and may be negative; a little ‘grandparenting’ perhaps, and some dubiously relevant ‘advice’; but does that pay for the food and the space?

(*  mmol total cholesterol per litre blood)
(**  There are many types of familial hypercholesterolaemia; the most common by a factor of 2 is a defective LDL-receptor, which presumably hoicks LDL particles out of the circulation and into some (presumably) removal pathway.) 
(***   My erstwhile colleague Loranne Agius suggested that the ingestion of excess carbohydrate feeds into fat production in the liver which requires cholesterol for its excretion.)


                  PLEASE COMMENT

Tuesday, 20 June 2017

BT help, BT — help!

BT help, BT — help! 

I wonder if readers will think I am paranoid in seeing a possible malfeasance in the following story.

I get a crescendo of letters and emails from my Internet Service Provider (ISP, namely BT) suggesting I upgrade to 'Infinity Broadband'. (I ignore these as the 15 megabit/s download rate is sufficient for my needs). The last email from BT said they would waive the conversion fee of £50 if I decided to upgrade before 23rd June. Then my hub becomes disconnected from the internet for two or three hours on Sunday afternoon, which is distressing because we spent several wasted hours trying to transfer money in Mexico. Then we are connected again, till Monday noon. Then disconnected again during Monday afternoon when the Mexican banks become open (BST+6hrs).  I phone the helpline and a young welsh woman spends some 45 minutes “running tests” all of which come up negative. So BT say there is “no fault” and therefore no way they will replace or upgrade my hub free of charge. 
The only remedies she could offer were (a) to replace at a cost of £50 the hub(1) I currently have and remain on the same monthly contract as at present, or (b) upgrade ‘free' to a new hub(2) and contract at a considerably higher monthly cost, or (c) a mixture of the two whereby I pay £20 to come onto a moderately raised monthly rate. 

I say there certainly is a fault; and the service, for which BT and I are contracted, is failing, with no apology from BT and no mention of compensation. Not only that, but BT has failed to find the fault, and thereby wasted another hour of my time.