Steroid use and Roid Rage

Forty years ago I was a half-decent weightlifter (olympic weightlifting, British student team ) and very proud of my strength and speed. Back then, as is well known now, anabolic steroid use was widespread in the strength sports and one of the reasons for me giving up was a personal unwillingness to use the steroids to improve my performance.

The Guardian today (22nd January) ran an article by Steven Morris describing the abuse of anabolic steroids by a million UK ‘gym-bunnies’ of all ages from too young to too old. They are not taking them for a competition advantage ( it’s actually quite hard to do this as drug monitoring makes it a bit tricky) they are doing it for narcissistic reasons.

Personally, I am not in the least surprised by the article, mere anecdotal observation as a school teacher has had me saying “goodness is he steroid pumped?” or for females “ that’s looks like a steroid rash not acne” on far too many occasions. You see, I recognise the effects of steroids at a glance from years of training in the weightlifting world.

So far, so good, ‘bully for me” you might say, “what observation skill!”. But this is serious, steroids are serious. We were very used to steroid rage, “roiders” they were called. It was well known that one of the world’s greatest lifters needed a team of minders with him during competition in case he exploded. Trashed hotel rooms were common. Even at my college we knew not to get across an olympic field athlete and who became a lot safer when he retired!

Over the past years, when a brutal attack has taken place which is featured on the media, the first thing I look for is to see if he is ( in my observation, a ‘roider’). Explosive, sudden, often unheralded violence usually accompanies  descriptions of the perpetrators who range from baby-sitters to gang-enforcers to terrorists. Tip, check out the neck first.

The point of this short blog is to highlight the the psychotropic dangers of steroid use. You might be very proud of your physique and power but be unaware of the unexploded bomb that is you. Or indeed the Tony Soprano image  may be why you are taking steroids in the first place. Either way if Steven Morris’s million users is anyway near the mark this is a serious problem and personally I would ask for anabolic steroids to be classified as a Class A drug.

UK Computer Cheats

As a final comment on computing in UK schools Ofqual has cancelled mid-year all non-examination coding assessments from all 1-9 GCSEs due to wide-spread cheating by teachers and students in the, now legacy, ‘easier’ exams taken this summer.

Yes cheating was and is widespread in GCSE coursework generally; teachers have become corrupt as a result of, amongst other things, having their pay linked to their GCSE grades through their annual performance ratings. Computing teachers simply barely exist at all and press-ganged ICT teachers make as much use of the online forums containing the answers as the kids do ( as Ofqual found out from the IP addresses).

Unfortunately for computing it is almost impossible to assess coding skills through written exam papers, hence all except the IGCSE have programming coursework … or rather did have coursework. All coders I know, code with one screen web-linked  open on StackOverflow, another on the docs and one on an IDE(integrated development environment) to format and debug as you go. None, as far as I know, do it all with pencil and paper like I did with punch cards in the past.

I moved my computing classes in 2016 to the IGCSE (International GCSE) run by Cambridge board. No course-work and deadly dull but we saw a lot of this coming. The sheer difficulty of the new ‘hard’ 1-9 syllabuses put us off, god knows what the ICT teachers thought. The assessments I saw were obscure and difficult. It is blindingly obvious that this level of challenge will produce almost universal cheating.

Put yourself in this position:

you have been teaching ICT successfully for years leveraging your MS Excel skills ( the envy of your colleagues indeed) and still keen enough to attend a three days of Python training to upskill into the coding world;

you work in an bully-boy Academy/Independent school with a ‘no one fails here’ *ethos teaching Y11;

your increase to the higher tiers of pay depends on your performance ( ie the grades);

the GCSE suddenly gets a lot harder.

Enough said.

The UK gov has said in its budget this Autumn that it will recruit 8000 new computing teachers … good luck with that. I’ll say it for the third and mercifully final time, (I retire this year) … computing in schools is finished. Ofqual delivered the coup de grace this week.

UK School Computing is terminal (official)

It’s official UK school computing is dying before it could even toddle.

The Royal Society reports this week:

• Across the UK,  11% of students in England took GCSE computer science
• 20% were female and the figure fell to 10% at A-level

Anyone who reads my blogs will know that I have been warning for some time that Computer Science is going to fail to establish itself as a subject in schools. There are three problems encapsulated in the bullet points above but for the time being I’ll let those points just hang there to be fully absorbed in all their bleakness.

At the school I teach we offer Computer Science at GCSE and A level and introduce it in Y6. There are two of us in the department both of whom can code to professional/hobbyist level in two languages.   Girls make up our very best students from Y6 but fail to opt to do it for GCSE (see above); forty years separates me from my colleague;  I will retire this year and my colleague from Eastern Europe will leave after Brexit.

We struggle to work out exactly what the exam boards want for their wildly varying syllabuses and our subject is the most expensive in the school due to the small number taking the subject compared with Geography or History for example.

I write the anecdote above because it explains everything. There are vanishingly few UK teachers between 30 and 60 years old; there is little to no substantial training for existing teachers to fill that gap; the subject appeals to those with the geek mindest which means a small uptake and a shortage of girls and finally this means it’s expensive - schools are short of money by the way.

That’s it folks, stop the hand wringing, none of  the above will be solved anytime soon.Even if you inject loads of cash we’ll just buy toys with it and the training courses will simply prove to the trainees that this is not for them.

And if you (misguidedly) make it ‘girl friendly’ you’ll patronise both women and the subject with pink-eco-friendly-code ... even ‘relational’ databases are so yesterday.

The computer-trained Euros are going home and the ZX80 generation are dying off. Just get over it and think afresh.

There is a solution, and computing should lead the way. UK is a third world country wrt teaching computing so we need third world tech solutions. All schools have broadband and whiteboard. The exam boards themselves should directly employ teachers  to deliver lessons to any signed up school in the 4pm to 5pm slot: done. Google classroom will provide the glue but what about ‘marking’? I hear you say. Don’t be daft, do you want to get rid of the teachers over again? .

The End of UK School Computing 2

Recently I wrote a post in which I argued that the much trumpeted reboot of computer science in UK schools to replace the mocked ICT qualifications was going to end in tears.

Well, now into my third year of teaching the new Computer Science syllabuses, I am more convinced than ever that it’s all gone horribly wrong. Being a generous soul I give it two more years.

Here are a few problems to mull over:

Raspberry Pi: what a wonderful British Linux machine this is and what a glorious world it has opened … but for whom? The school children it was aimed at? Not at all, the Raspberry Pi Bs are all in a drawer. Pi sales are very healthy indeed but worldwide to hobbyist crusties like me. It’s easy to see why, just look at the syllabuses.

The syllabuses at GCSE and A level are very diverse especially with regard to coursework and assessment. One GCSE syllabus had substantial coding exercises in their exams without any access to an IDE; one has no coursework;  another syllabus had 60% of the final marks as controlled assessment (class-based project work under ‘exam conditions’) one produced a 9-1 GCSE syllabus so difficult  Ist Year undergrads would respect it.

All this is not you may say exactly the end of the world, maybe the lack of consensus is merely unnerving but you can at least pick a syllabus to suit taste and ability. However what follows is more serious.

Few take CompSci at GCSE, AS and A level. At GCSE the numbers rival  those of German GCSE and for those in the business that will tell you all you need to know. Of those few, a fifth are girls. Additionally post 16, most  who start CompSci abandon the subject after taking the AS in Y12 leaving  a very select cohort to be ‘norm referenced’ into grade bands. In other words a good student by any objective criteria may well get a mediocre grade by comparison with uber-geeks.

However you view the above situation it means low numbers of mostly boys take CompSci qualifications. Low numbers mean very high costs. This can be sustained for a few years as a subject is introduced but not long term, budget cuts will see it off.

Finally, there is a teacher shortage in general, a STEM teacher shortage specifically and a dire shortage of CompSci teachers in particular, most of whom in any case are ICT teachers who have been pressed into teaching the most arcane of subjects having been offered a three day Python course. A specialised teacher shortage also translates into a shortage of specialised exam moderators which is death to quality control and so to customer satisfaction.

CompSci is great to teach don't get me wrong, it’s just I don’t think this model will fly. The National Project to create coders rather than MS Office users won’t be achieved this way. This begs the question ‘is there any solution?’

I think, and I think I said this years ago, that we need a technical baccalaureate post 16. An academic artisan a unique UK oxymoron. Maths, Design and Technology and Computing in one qualification worth two current A levels. Until this happens we will be stuck in a groundhog day of ‘more of the same’ post 16 ‘academic’ qualifications, we need more humanities specialists don’t we.

Diesel fumes are good for your mitochondria.

A hot topic for urban dwellers is exhaust emissions from diesel cars. Specifically the debate, centres on  NOX emissions and various figures for the number of premature deaths resulting from their inhalation: The Guardian reports 38,000 globally die each year but are not specific as to whether this is due to NOX from diesel cars or more generally from particulate or hydrocarbon inhalation concomitant with car use.

The good bad and ugly of exhaust emissions often, usually get conflated. First up, particulates, especially the fine particulates are bad, potentially very bad. Larger visible particles from inefficient combustion (soot) will damage lungs and exacerbate all pulmonary disorders but the very fine, near invisible particles can penetrate the blood brain barrier and even damage mitochondrial function. Particles such as these are as much a function of wear on the modern ‘safe’ fat, soft tyres as of they are of exhaust pipes which have particulate filters fitted. But what about NOX?

NOX stands for the oxides of nitrogen, it’s unfortunate that NOX sounds like noxious for memetically this is a very potent thematic link to its deprecation. The oxides of nitrogen from exhaust emissions are N2O, NO and NO2 , traditionally called nitrous oxide, nitric oxide and nitrogen dioxide respectively. N2O is a potent ozone depleting gas which persists in atmosphere for over a hundred years until photochemically oxidised to NO. NO2  is a choking dense brown gas which dissolves in water to form nitrous acid and ultimately to nitrites and nitrates.

This brings us to NO, nitric oxide, NO is the primary nitrogen oxide of exhaust emissions1. And here’s the thing … nitric oxide is good for you! The list of good stuff is long and varied so here are three of the best.

The ancient Egyptians were famed for their extensive use of Kohl ( galena based) around the eyes of men and women. They had good medical reasons for doing so, the local release of NO would have made good use of its anti-bacterial properties reducing eye infections and parasitism in a region where this was an endemic health risk. Bringing the story up to date 2017 saw the release of a nitric oxide based cream for treating psoriasis. The list of topical applications of nitric oxide in treating skin diseases from eczema to acne is long.

Nitric oxide has important internal biological signalling functions. Nitric oxide causes large vessel vasodilation naturally in the body improving circulation generally and which has encouraged the sports community to explore its potential in performance enhancement ( before it’s banned I guess).

Nitric oxide appears to be one of, if not  the major signalling factor in mitochondrial biogenesis2. New, young mitochondria are the holy grail of the aging research community as has been mentioned many times before in this blog

You will get the idea by now. We should be looking at urban populations for better skin, athletic performance and longevity, all down to nitric oxide from the modern diesel engine … if the particulates don't get them first, even electric cars have tires.

1. https://www3.epa.gov/ttncatc1/dir1/fnoxdoc.pdf
2. http://jcs.biologists.org/content/119/14/2855

Overclocking, mitochondria and aging

Overclocking Mitochondria.

‘Overclocking’ is a concept well known to computer-game enthusiasts. Simply put, they can increase the performance of their computer by speeding up the CPU ( central processing unit) or the GPU (graphics processing unit) by increasing the clock speed (instruction-cycles per second). They do this essentially by upping the voltage supplied to the chips …  upto and including the point where they becomes too hot and inevitably unstable. Typically, such voltages are between 3 and 5 volts and CPU cycles run at many MHz (million cycles per second). The ‘free’ extra performance is much prized by ‘overclockers’ with equally serious cooling systems and a penchant for breaking things.

Mitochondria have somethings in common with CPUs. They too are cycle driven electronic devices;  their cycle is called (variously) Kreb’s Cycle, the TCA cycle  or the Citric acid cycle. As it cycles, it fetches acetyl ‘food’ molecules from its surroundings spewing out waste water, carbon dioxide and heat as it makes ATP: magical, universal, ATP. ATP in turn is used to provide the free energy needed to drive all negative-entropy biological processes such as synthesis, repair, nervous conduction and locomotion. It makes over 100 ATP molecule per second which is about 3Hz in computer parlance* It does this with normal (trans-membrane) voltages between 110 and 150 mv ( 1/10th of a volt), 140mv being associated with optimum ATP efficiency.

Overclocked mitochondria, like CPUs fall into two categories; working well under conditions of high demand and just broken. The former would be the case say for  substrate-stimulated mitochondria using molecules such as glutamate and malate which speed up the TCA cycle and raise membrane potentials to 180mv. The latter would be for example hyper-polarised mitochondria found in cancer cells. These do not produce any ATP at all and are effectively inactive. They have membrane potentials of 220 mv, over ⅕ of a volt. This is put in perspective when 200 mv is usually recognised as the upper limit supported by lipid bilayers before breakdown as a result of exceeding the dielectric capacity.

Computer CPUs and mitochondria, not unexpectedly work best in their ‘Goldilocks zone” just the right amount of volts! With regard to mitochondria, very low membrane potentials, flrting with depolarisation  are associated with cell death, enlarged mitochondria and fewer cristae. The opposite seems to be the case, higher membrane potentials are associated with smaller mitochondria with many cristae …  and possibly with the inhibition of cell death whic intriguingly this may be the ‘motivation’ of the cancer cell’s hyper-polarisation of mitochondria thereby turning off the mitochondria’s ability to kill a rogue cell.

Exploring The Goldilocks Zone

We can downregulate (or even destroy membrane potential) and speed up the cycle by increasing metabolic demand or by using natural or exogenous uncoupling agents. These include the natural uncoupling proteins (UCPs) and chemicals like DNP ( dinitrophenylhydrazine) …  too much of these will uncouple the mitochondria and cause complete collapse of potential …  followed by cell death.

Conversely, membrane potential can be increased by stimulation (without extra metabolic demand) using substrates such as malate and glutamate salts or as mentioned earlier by blocking ATP synthesis.

If we assume operating at a level of metabolic demand which reflects good levels physical activity, nervous activity and tissue repair activity, it would be good if our mitochondria were operating above minimum ‘tick-over’ thresholds ( 108mv). Otherwise this would mean that increasing demand further on these mitochondria might depolarise them ... with disastrous effects. A capacity to work hard should be reflected best in the 150-180 mv range, probably the higher the better. We know that cancer cells can achieve massive potentials of over 200mv when blocking metabolic activity but it’s not clear whether such overpotentials can be utilized when oxidative metabolic demands are being made, even so stimulated mitochondria that have not been uncoupled will show potentials of 180mv.

We also know that animals with lots of brown fat, the cells of which are thermogenic because they contain partially uncoupled mitochondria, also have longer life spans than those of a similar size (cf squirrels @ 20 years, bats @ 30 years). In these animals mitochondria typically still manage membrane potentials of 140 mv despite being partially uncoupled . Their cycles are running very quickly but generate heat rather than coupled to the generation of ATP

Finally we also know from the work of Bruce Ames a decade ago that stimulation of mitochondria with acyl-carnitine ( which will increase the cycles and membrane potential as for malate and glutamate) and they associated the stimulation with increased cognitive behaviour in aged rats.

As an aside they added lipoic acid to ‘mop up’ excess free radicals. This point is worth expanding on. Free radical production by highly active mitochondria was once the bogeyman in the aging world. Free radicals cause damage to proteins and DNA which thens needs repair/replacement. Free radical damage accumulation is still one of the most popular aging theories. My point of view is that all damage can be repaired if there is the free energy so to do. In effect this means if you have enough ATP available then repair is not an issue. It’s an entropy thing. So in other words, free radical damage that accumulates with age reflects a repair-free energy deficit not a damage surfeit.  This is borne out by the fact that it has been well established that higher metabolic rates ( ie higher free radical damage) correlates not with lower life spans but longer.

So, keeping mitochondria spinning within their goldilocks zone seem to be the trick. In an oxidative environment where ATP production is not blocked there seems to be no downside to high membrane potentials. However there is one fly in the ointment and that is mitochondria in poor condition need to be destroyed so they they do not divide and compromise the total cell population of mitochondria. This, as has been explored in  a previous blog, is achieved through autophagy which in turn is stimulated or signaled by low mitochondrial membrane potentials.

Outside the Goldilocks Zone

So far so confusing, what about outside of the Goldilocks Zone? Ultra high membrane potentials can be dealt with quickly. They can only be produced in intact, mitochondria in good condition and reach their maximum when metabolic demand is at zero. Like the pressure in a water line, it is at a maximum when the tap is closed. Otherwise they seem to be harmless. Low potentials on the other hand have major effects.

Complete depolarisation, the collapse of the membrane potential, usually results in the release of cytochrome c from the inner membrane of the mitochondria triggering the cascade of reactions that lead to cell death. It looks like flickering depolarisation may act as a signal or a label for autophagy. This potentially is a ‘good thing’ in that sub-standard mitochondria will be eliminated from the population. A flickering state could be triggered by high metabolic demand. For example in bats, which have exceptionally well coupled low ROS mitochondria have ultra long life spans of 30 years, remarkable for such a small mammal (cf rat @ 3 years), they only develop these mitochondria after they start flying: in other words after extreme oxidative metabolic demands are made.

Anoxia, ( low oxygen tension at altitude for example) causes both mitochondrial depletion and hyperpolarization. High altitude training of athletes results in fewer mitochondria within muscle cells but those that remain are better coupled.

Summary

Like many before me I am getting lost in the woods as it were. My overclocking analogy does not really hold for very long. CPUs cycle at a clock rate proportional to voltage but independently of external load whereas mitochondria behave more like simple electric motors which cycle according to voltage and load, according to work done. What has worked though is an exploration of mitochondrial voltage, it looks like there is an optimal voltage and cycle rate which generates enough ATP to keep the system working with an excess of free energy.

I think that mitochondrial stimulation and energetic loads must be important in preventing senescence, finding the sweet spot is the challenge.

Middle ClassLife Expectancy Falls: shock!

The ‘ever increasing’ life expectancy of men and women in the UK has come to a shuddering halt according to University College London expert Sir Michael Marmot.

Austerity measures got the blame, but I don’t think that’s so as analysis of the figures show that the decrease is down to the middle-classes. Now that is shocking; this after all is a demographic that is notoriously health-aware, a group that devours articles on diet, exercise and lifestyle. Worse is to come, the data show that deaths from dementia make up a significant portion of the decrease.

Alongside the above comes data that supports the age-related cognitive benefits of the Mediterranean diet  and (trendily) the Nordic diet ( basically fish, berries and apples).

So what is going on?

I think it’s simple. Middle Class people over 60 tend to follow the advice from their Sunday Supplement style gurus and local GPs. This this means that they are:  a) most likely to have reduced the fat and cholesterol in their diet, b) are most likely to take statin prophylactics to keep cholesterol down, c) most likely to take ‘precautionary’ medication for borderline ( usually systolic)  hypertension and d) use sunscreen to block harmful UV rays.

This is to my way of thinking a ‘perfect storm’ of disastrous choices.

Good diets, by consensus,  are very high in cholesterol or the progenitors of cholesterol: fish, olive oil and fungi topping the list. Good diets are high in fruit acids, citric (in citrus fruits) malic (apples) and both in tomatoes.

1)We need cholesterol for so many functions of our body but principally for electrical integrity in the nervous system and the mitochondrial energy generation systems. We need cholesterol to make Vitamin D, a well recognised vitamin important to nervous function, which is synthesised when its cholesterol-derived precursor is exposed to sunlight.

2) Citric acid and malic acid are well known stimulators of mitochondrial function.

3) Mild hypertension is an age-related adaptation needed to supply oxygen and nutrients ( see above) to the brain as the circulation system becomes more resistant to blood flow with time.

So here’s the deal. Let’s deprive the brain’s neurons and nerve fibres of their fatty raw materials, their mitochondrial energy stimulants and even oxygen …  and do this deliberately by limiting them in the diet plus with the aid of chemicals such as statins, calcium channel blockers and sunscreen.

I’ve just read the UK pension age for the Generation Y has been raised to 68. I just hope they stay away from their GP!