Monday, August 29, 2016

A new study showing that genetically determined levels an anti-inflammatory (IL6) are linked to intelligence and personality changes, and caused by disease levels.

This is fascinating. It makes sense, that it should be more important to survive pathogens than to be clever, but the effect on so many things is remarkable.

Who'd have thought that on part of the immune system, an anti-inflammatory, interleukin-6 (IL6), should have such a powerful effect on personality, with high-levels of conscientiousness, openness and neuroticism all more common where disease burdens are lower.

It also makes sense that optimism should be linked with a lower disease burden.

I suppose it's less of an appealing set of results to those who put a high store on use being responsible, through 'free will', for the way we are.

It seems a bit perverse that dim, unadventurous, impulsive, bovine types should be more attractive and, thus, fecund, in places where there's a high level of infectious disease - but there you are, that's the way it is, because of IL6... at least that seems the most reasonable direction of causation for a genetic trend.

Still, IL6 doesn't seem to have any effect on agreeableness or extraversion, so, maybe these people are hail-fellow-well-met types to make up for their otherwise dull approach to life.

It's a very good reason to be careful in the use of anti-biotics and earnest in looking for replacements - we probably spend too much on cancer research compared to pathogen extermination research.

This also provides some support for David Horrobin's view that schizophrenia was related to the immune response and could be ameliorated by essential fatty acids in the diet. -- I've checked and Omega-3 does decrease IL6 levels significantly. ( )

Saturday, September 5, 2015

Wealth and wellbeing - Heraclitus' balance - Epicurus' eudaemonia?

The statistics office in the UK has just produced the figures for life satisfaction for 2012 ( ).

The Financial Times (FT) has interpreted this as showing that the richer you are, the happier you are. Well, they would, wouldn't they.

The good news for those who do not think wealth for the sake of it is a good thing, is that it isn't quite that simple. There is still room for what Epicurus called 'eudaemonic' (human flourishing) and for Heraclitus view that life is about balance and flow, not extremes.

Here are the graphs:

What about decile 7? -- from ONS
You can see the one that the FT has latched on to. The top left shows 'Life satisfaction' against wealth, and shows it is lowest for the poorest, and highest for the richest.. Not quite, though, notice the bump at D7, which is more satisfied than D8, even if not as smug as D9 and D10.
Reported smugness isn't everything there is to happiness, though.

At the bottom left, self-reported happiness shows another bump for D7. The three happiest deciles are D3, D7 and D10. For some reason, D8 and D9 are over twice as unhappy as D7.

A sense of worth is very important to eudaemonia - and, there you see, again, at the top right, D7 is the anomaly, happier than both D8 and D10, and about as happy as D9.

Finally, what's the point of having lots of money and being anxious? The most anxious people are the D3s, which offsets their reported happiness. Yes, the very richest, the D10s, are less anxious than most.... But, the least anxious of all, almost half as anxious as the D10s, are the D7s.
On every measure, there seems to be something special, something closer to eudaemonia, than all the other deciles.

Who are this happy few? Well, the centre of the income group is a gross income of £41,123, or, more sensibly, an income between £37,700 and £45,575. That was in 2012, when the average gross income was £39,200. In percentage terms, this adds up to +/-16.3% of the average gross income.
In terms of disposable income, this is +/-12.9% of the average disposable income, that was £29,447, or, in the range between £28,482 and £33,280.

This looks much more reasonable than the FT's notion that the richer you are, the better.

To have the best balance of satisfaction, happiness, and a sense of worth, with the least anxiety, you need to be round about the average income, about 10% of it.

As Goldilocks would have said, not too much, and not too little, just right.

Friday, September 26, 2014

The Stedelijk Museum Amsterdam - I'd not recommend it.

I was at the wonderful, renovated Rijksmuseum only a few months ago, and I've can't remember how many lovely visits I've made to the van Gogh, so a change seemed a good idea. The Stedelijk was not a good choice - I'd recommend against going, actually.

They've a big exhibition of pictures by Marlene Dumas. I'd never heard of her, not that surprising. I looked her up and she's a South African, based in Amsterdam. Clearly she's very good at marketing.

There were two or three good pictures - this portrait, on a vast scale, was one I thought OK:

Mostly, though, they were large, messy, monochrome scribbles with much emphasis on genitalia, for no reason I could see. Stuff that'd be find for student practice work, but not the sort of thing you'd want to pay 75€ to see when on your hols with excellent art only a few hundred metres away.

The rest of the gallery was variable. There is a nice van Gogh, an interesting Kandinski, a few walls with vivid blocks of colour and lots of indifferent messes. 

There are lots of 'found' objects - the main question they raise is why they weren't just left there when found.

There are a few rooms of furniture and household goods - the furniture can't be sat on, it's in glass cases, so you can't tell if it is as uncomfortable and impractical as it, mostly, looks.

I liked the kettles, but I've a particular interest in the evolution of the kettle. I liked a few porcelain pieces, below.

The highlights (pretty well all of them):

Can you see the magnificent cockroach?

A most unpleasant woman

I didn't want to listen to her at all. At Citizen M, you breakfast at long refectory tables, sadly not under the rule of St. Benedict. So I had no choice, she sat opposite me.

I don't agree entirely with the St. Benedict, 'Scurrilitates vero vel verba otiosa et risum moventia æterna clusura in omnibus locis damnamus et ad talia eloquia aperire os non permittimus.' goes too far, certainly. I'd hope that even Trappists were allowed the occasional joke. He was right about silence at breakfast though.

After a long, loud discussion with her neighbour about some business they're doing in Amsterdam (she's away from home, leaving her husband to look after the two children - I had much, too much information!), she mentioned that it was their tenth wedding anniversary - and she had heard nothing from her husband.

One of her companions (pan au chocolat - so a genuine companion) suggested that he might have some nice secret surprise in store for them.. 'No! I know him and he's not like that - not like that at all'   the harpy replied, with no thought required.

A few minutes later a message came through on her 'phone. He's sent me a message, the disappointment at her anger coming to an end was evident, obviously his mother has reminded him.

It seemed completely beyond her ken that it was not her wedding anniversary, but their, shared, wedding anniversary. She hadn't any notion that, being away, on the anniversary, was her failing and the least she should be doing was getting in touch with him first, and early, to reassure him that all was well and she'd remembered.

In fact she seemed to think that the only reason for the event at all was for her to get presents, the most sought-after being a metaphorical knife to dig into her husband's ribs, as she goaded him for his forgetfulness of the anniversary.
It's possible that the chap in question is also a nasty piece of work - an estate agent, serial or mass murderer (soldier or free-lance), or a prison warder or framer of laws against victimless crimes - who knows. If he's a decent human being, he certainly doesn't deserver that treatment.
I hope he's rid of her soon, poor fellow. I know nothing about his qualities or achievements - only hat he has a very poor taste in women and, in at least one area, an inability to make sound judgements.

She listened in to our quiet chat about the day, and interrupted us to advise going to the Stedelijk museum Foolishly, I ignored the evidence in front of me and went. I wish I hadn't, what on earth made me ignore the obvious - how could such a woman have any aesthetic taste?

Harpy - Matthew Lewis -

Friday, March 23, 2012

More than this?

Bryan Ferry of Roxy Music answers the question:

More than this, there is nothing.

Quite. What could there be? Why would anybody want it?

If you realise, and consider that everybody you meet, even the beggar in the street, I living, consciously, the only life they have. Everybody, at the moment you see them, in the Café, on the road, in the hospital, in the school, walking on the mountain, eating their breakfast is, having the only moment of their lives that is real - now. How can you imagine that there is any need for more - than this?

This. Now. This-now. The moment between memory and anticipation, the instant where all our past makes us what we are, just now. It cannot be bettered. Even if this present moment might be dull, apparently, or painful, or sad, or just mundane - it is everything. There is not, and cannot be - more than this.

Yes, of course, we might have imaginings of the future, ambitions, dreams, plans, expectations, but, even if all, or none, of them come to be, it still remains the case that there is only, in the absolute sense of it, this. Now. This moment - and, no matter how long, or short, or happy, or sad our lives that will always be the case - more than this, there is nothing.

It might seem to be a recipe for defeatism, for regret - it would be nice to think that there might, or could be, more than this, but, a moment's thought shows that it couldn't be. It shouldn't be, and we wouldn't want it to be. This is. This is complete, and sufficient for any life.

Yes, it might be less than this. If we don't realise, at the time, that there is no more than this, we may live our lives in pointless, fruitless, and depressing anticipation of the 'more' that we anticipate, or hope for. We'l l always be disappointed...

Unless, realising that there is no more than this, we make it our aim, our reality, our dream to be just this, now, what we are and what we feel at this precise moment. If we fail to do this, but think of ourselves as what we were, or what we might be, then, no matter how wonderful those thoughts, no matter if the best imagining become true, we'll never appreciate them. Because, the only magic, the only delight, the only pain, the only part of being real, really real, is being here now. Exactly at the moment - not missing it, not pretending that it isn't here, but being in it, part of it, having it as the understood, precise and only moment when we are actually alive.

How simple it is. How odd that it should be necessary, or seem necessary, to point this out. Isn't it obvious?

When we meet another. Whether it's a moment of intense togetherness, or a glimpse into the eye of a stranger, we share our aloneness, in our moment, in our life, with another. That exit from solitary contemplation into being a part of another's life, is precious. Precious beyond our moment of being ourselves, in this moment, just now. It's an opening to another universe, another human - being a being more than just me, being a human being, being a moment in another life that, also, like ours, is made only of just now.

There is nothing new, or surprising, or odd, or wise about anything I've said - it's as original as breathing. What's odd, and in need of explanation is, rather, how far we distance ourselves, through illusions, from understanding this. Why is it that we need an explanation? Why do we find Bryan Ferry's song profound, rather than obvious? Why do we build such edifices of rationalisation to pretend, to ourselves, that anything other than this, and now, matters?

I'm not, and this obvious set of remarks isn't supposed to make you feel less than you are - you shouldn't feel upset that your hopes, dreams and memories are less meaningful than how you are exactly now. It is rather the other way around - our hopes, dreams and memories are there precisely to make now, this, exactly as precious as it is.

It's peculiar, really, that we need meditation, philosophy, the words of the Dalai Lama to tell us what is obviously in front of our nose:

“Be kind whenever possible. It is always possible.” ~ Dalai Lama

“If you want others to be happy, practice compassion. If you want to be happy, practice compassion.” ~ Dalai Lama

Compassion is only the result of seeing another, any other, conscious being and seeing that he is in exactly the same moment of the same amazing thing - conscious life - as you are.

Monday, December 12, 2011

Europe's Problem with rules

Why only the UK has problems with EU rules:

The Belgians make the rules.
The French follow rules that suit; eg. Champagne & Camembert.
The Germans follow all the rules, but only in the German translation.
The rest know the rules exist but are too small to attend to them all.
Only the English actually follow all the rules.

Friday, August 28, 2009

A slimming drug that actually works?

Slimming with no diet or surgery – but not snake oil??

Yes, actually this really is a cure for obesity. It works and is undergoing clinical trials at the moment. You don’t have to believe it – look up the research referenced below.

Nothing that works is without side effects, so this article considers possible problems that there might be with this wonderful cure for a massive problem (if you excuse the pun!). It is worth mentioning that the author has no links to Zafgen, the original researchers, the Venture Capitalists or any other interested party. Also, the author is a strong supporter of this drug as, almost certainly, the best cure for this epidemic that has been discovered.

The cure is simple, you’ll take a drug over a few months and loose up to a third of your body weight, with no need for diet, exercise or surgery. Amazing, but true. The weight should stay off, maybe not for life, but certainly for a long time.


It's been claimed many, many times before, and huge amounts of money have been made pretending that a cure has been found to obesity. Snake oil of all sorts has been poured into the slimming industry, all to no avail. People might lose weight for a while, though taking up horrible slimming diets, exercising to unhealthy excess or any of a number of even crazier notions - liposuction, for one, sucking superficial fat out of the body with a vacuum cleaner.

Then, back in 2004, Mikhail Kolonin, made the break that would become the magic bullet of the 21st Century. His paper 'Reversal of obesity by targeted ablation of adipose tissue' can be found here - Kolonin had been researching a method of curing cancer and had the brilliant idea that it might work for obesity.

His research was funded by a charity that was not in a position to exploit this breakthrough, and so it sold it to a company called Zafgen ( that is handsomely funded by a group of Venture Capitalists. Zafgen hope to have the results of the first Clinical Trials early in 2010.

How will this Silver Bullet cure obesity?

All the cells in our body go through a natural life cycle. For us to be healthy, they cooperate with the rest of the body, so much so that, when the body asks them to die, they do. When this cooperative mechanism breaks down, and cells refuse to die when asked, we develop cancer.

The natural death of cells is called apoptosis. The request is made by messages encoded in chemicals called peptides. Kolonin's team had been producing peptides that were aimed (targeted as in his article title) at the blood supply (vasculature) of cancers. Kill the blood supply and the cancer dies. That was the idea. Turning this to fat, he found a peptide that, in mice, would kill the blood supply to their white fat deposits (we have brown [good generally speaking] and white [not good in quantity] fat in our bodies. They used specially bred genetic mice that grow hugely obese and, with this method, they were able to get them to loose a third of their body weight in a few weeks and, apparently remain perfectly healthy. The method is particularly good as it removes fat from around the vital organs (liver, heart, stomach) not just external fat (as something like liposuction does).

To adapt this to people, the right peptide messenger had to be developed and then carefully tested to make sure that it did not, for example, damage the brain (which is quite a fatty organ because the brain uses a lot of energy to think). Zafgen has been working to do this, and the clinical trials should show if it works and if there are any unexpected and dangerous side effects.

The Obesity Epidemic and profit

According to the World Health Organisation (WHO) there are over a milliard people who are defined as ‘obese’ on the planet. Each one of these is a possible target for this drug. So you can see why the Venture Capitalists have been piling in to fund this. If the drug sells for only $10 a treatment, then the research, manufacturing, distribution will be paid for easily, and Zafgen and its backers will be extremely rich.

Danger 1: Marketing and off-label prescribing

That’s not how it is likely to play out though. The literature on Zafgen’s site suggests that only the extremely clinically obese will be targeted for treatment to begin with. This makes sense, for them obesity is not just a life-threatening condition; it reduces the quality of life hugely, so it is only right that they should benefit from this huge breakthrough.

Also, since these patients are already at high risk of death and disease, because of their weight, they are unlikely to be able to sue Zafgen if something seems to have gone wrong. How, the lawyers will ask, can they prove that it’s the slimming drug and not one of the many obesity related conditions that has led to their death or deterioration? A difficult case to prove.

So it’s safe too, from a legal risk perspective.

What’s the problem then?

Well, to sell the drug to just this group of people, Zafgen can apply to the FDA, and other drug licensing bodies, for a license for the drug that states that it is only for use in people who are extremely obese – and only tested on such people.

Now, if this license is granted, and on these narrow terms, what is actually going to happen?

Obviously, literally millions of people will want the drug and will pester their doctors to get it for them. Their doctors are likely to comply and order the drug. But they won’t be able to prescribe it, as licensed, to people who are simply a little overweight, or want it to slim down to get that acting part, or to keep their pilot’s license when they’re not even classified as overweight, let alone obese.

So, will the drug be refused? No. The doctors will be able to do what is known as off-label prescribing. Based on what is called their ‘clinical judgment’ they will be allowed to prescribe the drug as for ‘off-label use’.

What’s the problem with this? The patients get the drug.

The problem is liability. Since the drug is prescribed ‘off-label’, if anything goes wrong, it’s not Zafgen who will be prosecuted, or the FDA for that matter, they’ve only claimed that it will work for extremely obese patients. Patients who have dangerous side effects will only be able to sue their doctor.

This is good news for Zafgen and the Venture Capitalists. Even though ‘off-label’ patients are not benefitting from, or protected by, the research and clinical trials (because they were only designed to test the target group), they won’t get a discount. They will still have to pay full price to Zafgen. So Zafgen gets a risk-free profit. Very nice indeed!

Not good news for patients. The doctor may not have the insurance cover to compensate for the problems – and the problems won’t be listed as side-effects of the drug, because they only apply to ‘off-label’ use. So a major side-effect might be hidden for quite some time, allowing even more people to suffer from it.

So, if you are not in the target group, you have good reason to fear being prescribed the drug off-label – there might be some terrible side effect, that doesn’t happen to extremely obese people, but does to those of more normal weight. You will be, in effect, the guinea pig when you take the drug – but you won’t be part of a proper trial, so, if you die, or are made ill, it won’t contribute to saving other people from taking the drug in the wrong circumstances.

Danger 2: What might these side-effects be?

The short, and truthful, answer is that we won’t actually know until thousands of people have suffered them. We can only speculate on possible side effects, knowing how the drug works. So, speculating, what might these be? Here’s a list of some possibilities, it is not exhaustive:

1. Need for surgery. Rapid, and extreme, weight-loss can leave the skin hanging loosely from the body, and this loose skin can be prone to infections. This effect is found in people who loose weight through bariatric surgery today. The cure is surgery to cut away the excess skin. This surgery is expensive and, like all surgery, risky. So you might pay your $10 (or, more likely $2000 – the Venture Capitalists are unlikely to charge a price related to the cost of the drug, they’ll want to charge as much as the market can stand), but then find that you’re exposed to costs of $30,000 or more for the surgery.
2. Depression and Suicide. Loosing weight can reduce the amount of serotonin in your body, which can lead to depression. If somebody is susceptible to depression already, this could lead to suicides. If the drug is used off-label, the risk is likely to be different from that of the extremely obese patients the drug has been licensed for. So it is possible that some groups might show high levels of suicide that would only be discovered some time later – again because of the off-label prescribing.
3. Drug and vitamin overdoses. Many drugs, including illegal recreational drugs, are stored in fat tissue. When fat is released in large quantities, suddenly, these dissolved substances are likely to be released into the body, potentially in large quantities. Cannabis, for example, is stored in body fat for many days, possibly weeks, after use. This stored drug could suddenly be released, leading to an intense and unexpected ‘trip’ that could arrive suddenly and be dangerous if somebody was, say, driving. Also fat-soluble vitamins would be released, such as Vitamin A [or other fat soluble vitamins [A, D, E & K], which can be lethal to the liver in large quantities, as those who have eaten Polar Bear liver have discovered – so deaths may result from this effect, particularly in people who may have been taking large doses of vitamins over preceding months.
4. Accidental overdose. In theory, the drug will continue to kill off white fat cells until there are none left. Brilliant, you might think, that would suit me! However, we need a certain amount of fat to keep our brain supplied with energy, as well as a reserve for energy needed for other exercise. If we had no white fat, we’d be in danger of a few things, high vulnerability to cold, extreme fatigue, possible black-outs that could only be fixed by eating throughout the day, maybe even needing to wake up at night to eat to keep energy levels up. The problem, again, is that dosage levels will be known and documented for extremely obese patients, but not for the general population or for those who are slightly overweight, so there is a danger, if the narrow licensing model is chosen, of accidental overdose where doctors, unfamiliar with the drug, give higher doses than required. There is also the danger of abuse, where somebody uses the drug prescribed for somebody else and gets an overdose inadvertently. It is not known if this effect would be reversible. It is worth noting that people who take too much will have hardly anything in the bottom and breast department, a side effect that most women would not find desirable.

What is to be done?

As stated at the start, this is intended to be a positive article, not just doom and gloom. So there are potential remedies. The first is for Zafgen to apply for a broadly based license that includes people who are not grossly obese, but only slightly overweight.

If this is not possible, the FDA should require Zafgen to sell the drug at cost, with no profit, if it is prescribed off-label. This would provide Zafgen with a strong incentive to broaden the license as soon as possible.
The FDA should also create a register of off-label effects, not just for this drug, but for all drugs, so that doctors who choose to prescribe drugs off-license can, along with their patients and the symptoms they have, be tracked.

Finally, the risks outlined here, and other likely ones, should be specifically tested with animal models and humans before registration of the drug.

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