Martes

Squirrel Nutkin Sciurus vulgaris is [right] cute but I haven't seen any [yet] hereabouts. It's partly because I see nothing hereabouts because, when I'm outside, I'm usually blundering about disturbing the peace with a lawn-mower or saw. But in the middle of last week, a cock-pheasant Phasianus colchicus strutted across the yard and before I'd found a camera he'd been joined by his hennie. These birds are more usually heard grackling indignantly as they fly away from intrusive galumphing people. So it was nice to see them, from the kitchen window, passing through in their own good time.

I've seen loadsa pheasants in my time; but never in all my born days have I seen a pine marten Martes martes. Although several of my naturalist neighbours have. On Sunday morning we were pottering about and a pine marten lolloped through the gate to the haggard and started exploring the yard as we watched from the kitchen window. It was amazin' mystic, wonderful to see this top predator making our home their own. What's that got to do with the native squirrel? You may well ask. Because they are both making a come back in the Irish Midlands and there is some evidence that forward march together is not coincidental. Grey squirrels Sciurus carolinensis were introduced from North America to Ireland in 1911. They are bigger and bolder than their red cousins and have spent the last 100 years displacing the reds from their habitat.

The argument is that red squirrels and pine martens have been living together since time immemorial and have come to an equilibrium in the evolutionary dance of life and death. Greys otoh are naive to that particular predator and haven't yet worked out appropriate defensive strategies. A recent study from QUB applied marten-smell to feeding locations and report that reds avoided such feeders after treatment whereas greys didn't. Fig 3a from that paper [R]. Fig 3c suggests that reds were more vigilant under the same conditions.

Another study from NUI Galway [PDF of original survey results] looked at the relative distribution of greys, reds and martens in 2007, 2012 and 2019. A lot of that data was crowd-sourced after an extensive publicity  campaign so that may cast some asparagus on the absolute numbers of reports [3,402 in 2019 up 20% from 2012] but there are significant differences in the proportions among the three species between the two survey years. On the face of it it looks like reds have gained ground in the Irish Midlands with a little help from the depredations of a resurgent marten population.

These studies were reported without any critical analysis by Richard Nairn in his Wild Wood book. Which is fair enough in a memoir. It's a pity I didn't get to referee either of these papers because, I would have devoted a day of my time to constructively picking apart the methodology and assumptions. With any effort at all I'll say a) If the hypothesis is that it is a specific pheromonal response to scent of martens, I would have used cat urine as a control rather than nothing at all. b) In the 3rd paragraph of the results of the NUIG survey a number of 3 [species] x 2 [years] contingency tables have been analysed with ChiSq. They have looked up the resulting numbers as if there are 3 degrees of freedom. But that's almost certainly not true. There are only 2 d.f. because once you've assigned numbers to #grey and #red then #marten is not 'free' to vary: it must be 1 - (#grey + #red). That's sort of okay, because using the wrong line of the table results in a more conservative test of the difference. Then again, if they can't do elementary stats correctly, critical readers are justified in giving side-eye to the rest of the study.

But here's an interesting anecdatum. Last year we had a plague of rabbits, really for the first time in 25 years. I constructed an elaborate [2x1s and chicken-wire] rabbit proof fence for the two ends of the poly-tunnel so that the rabbits were at least slowed in their depredations on the beans, lettuce and tomatoes. This year looked like being the same. A couple [pair, M+F, breed-like...] of rabbits were to be seen daily in the garden nibbling away at the greenery bold as brass. I would ineffectually peg small logs and large stones at them but I was girding my expectations for no cabbage in 2021. And then from about 3 weeks ago the rabbits weren't there any more and two weeks later a pine marten graces us with their appearance. Like Darwin's ruminations on the relative count of clover, bees, cats and mice; this is another example of my enemy's enemy is my friend.

Alzdoggle

There are two ways for MegaPharm to make money: sell a lot of pills cheap or service minority diseases for eye-watering prices. Ideally, MegaPharm, wants a common progressive degenerative disease which fails to kill affluent white-folks. There are a few which [✓]: heart and circulatory disease, cancer, Alzheimer's. Alzheimer's is particularly attractive because there is no cure, the symptoms are distressing, and it lasts for years. Every player in Team MegaPh has had a punt at an Alzheimer medication [primer previa] and pretty much everyone has dug deep in their R&D kitty and still come up empty.

The latest cap  thrown in the ring is Biogen's Aducanumab [-mab IDs it as a monoclonal antibody] which will be marketed as Aduhelm and received a new sort of appro from the FDA on Monday. This anti-body targets the amyloid plaques that everyone who can spell aluminum knows to be associated with the development of Alzheimer's. Associated with: nobody knows about cause and effect here: it is possible that nobbling the plaques is like throwing gasoline on a fire because the plaques are desperate but characteristic response to the underlying unknown cause of The Alz.

Any new med in the USA has to be approved by the FDA [Fud n Drug Admin]. Normally, MegaCorp has to show that a) the drug works ["efficacy" in the jargon] b) the side-effects, if any, a small compared to the benefits [safety]. Many of us will have experienced side-effects of vaccination in recent weeks, believing that these are going to be less offensive than a dose of The 'Rona, long-covid, intubation and death. The last step of the licencing process is for the drug company, here Biogen, to submit the results of two independent Phase III trials where the drug has been compared to placebo for the treatment of a large sample of people with early stage Alzheimer's. 

For Aduhelm, one of these trials showed that there were no statistically significant benefits, the other that the benefits were positive, but barely discernible. By the traditional standards of the FDA, this should have been enough: indeed Biogen should have owned the results and withdrawn to join the long line of might-have-been money-printers for Alzotherapies. But the FDA is barrelling on regardless of the evidence: "We decided that the accelerated approval pathway fits well here: it allows for there being some residual uncertainty on the drug's clinical benefits while making the drug available to patients rather than having to wait." FDA approval means that Medicare is obliged to pay for this treatment in eligible patients. The FDA reserves the right to pull the plug if the larger sample of treated people throws up even more adverse side effects and/or there is no demonstrable benefit. But FDA approval means that income is now being generated by Biogen during the roll-out. The company's share price bounded 50% higher on the news and the value of other companies known to have Alz drugs in their pipelines achieved a collateral boost. The guide price for 12x monthly infusions is $56,000 - ymmv depending on how well your insurer plays hard-ball. Even so, the actual patient and their families will probably have to stump up 20% of the cost of the treatment. Biogen is anxious to get this cash-cow a-milking because the tiny but lucrative market for Spinraza [Bloboprev] their successful therapy for SMA Spinal Muscular Atrophy is being challenged by Zolgensma [yest].

Side-effects?? 

• Painful brain-swelling - 40%
• small bleeds in their brain - 17%
• headache, dizziness, visual disturbances, nausea, and vomiting - the usual suspects

Who is going to be making a decision on whether to risk a painful brain swelling in an elder who is still able to have a conversation and is reasonably continent ? Unlikely to be someone who can easily fetch $50,000 out of their back pocket for the next several years. Even a $10,000-a-year "co-pay" would eat up all my pre-retirement discretionary income. It would probably be the difference between the kidder going to college or not. Nobody should have to make those choices even if the $50K brought the Elder back to playing soccer or scrabble with the grandchilder. But Aduhelm doesn't promise that; it hopes, with a following wind, to be able to promise a teeny amount of slowing in the rate of decline in cognitive function and a definitely reduction in the number of amyloid plaques.

But here's the thing; when it goes to market Aduhelm will start to bask in the kudos of the placebo effect - it will be as effective as homeopathy which works quite well for this very reason (so don't knock it!). A few anecdotes of Dad's improvement in cognitive function will start a cascade:

• families will demand
• docs will prescribe
• pharmacists will fulfill
• public will pay
• most patients will decline anyway
• sales reps will get bonus
• shareholders will need a bigger handbag for the loot

But the same benefit could be achieved by Big Red Pill Inc., @$5 a day to cover the marketing campaign.

Tnx to G for goading me to pay attention.

Arms Race

Due to my very expensive education, I have done my team some service in pub quizzes . . . until it came to the picture round. Then it is a massive fail because having no TV really puts the kibosh on recognising celebs: actors, newscasters, soccer players, pop-singers.  You will almost certainly do better:

me, I saw Clint Eastwood in Dirty Harry when it came out, and clips appear from time to time on youtube, so I get the cultural reference in the picture [L]. But I had to read the "answer" to twig that it's not Clint Eastwood but his fellow Californian Arnold Schwarznegger underneath the bouffy 70s hair. The rest of the scene is a [famous] still from the movie but Arnie's features have been deepfaked into the picture. Deepfake? barely 'eard of it of it until I encountered a geeky explanation by Mike Pound. In short the deal is to deconstruct facial features into 1s and 0s based on some 1000s of pictures of the same person - smiling, serious; looking up, in profile; in full sunlight, having a candle-lit dinner - and then apply those coordinates to another situation. Perhaps that other situation is occupied by an actor and perhaps that actor is doing something compromising. And then you have evidence sufficient to convince a hurried or unscrupulous tabloid journalist that there is a story that is worth ca$h to the creator. The tabloids don't care about any collateral damage meted out on the celeb.

Actually, that goose is only laying golden eggs for a window of time. As deepfake gets better at its illusions, plausible deniability gets to be ever more plausible. Nope! I was never in that swimming pool that picture is DeepFake. Which will drain the pool for traditional blackmailers as well. Good stuff!

In his DeepFake video, Dr Pound speculates on how, in a world of smoke and mirrors, we might be able to detect the authentic, The Right Stuff. One avenue suggested, ultimately futile, is to use AI gamekeepers to catch the AI poachers. It's futile because it results in an arms race of ever more complex, resource depleting, carbon footprinting, programmes with which the white hats outflank the black and are, in turn, bested.

In immunology, an Arms Race is the standard metaphor for the to and fro between the anti-microbial defenses of the immune system and the ingenious counter-activity of bacteria and viruses which, after all, are only looking for their place in the sun propagating their genes into the future. In the many discussions about life, the universe and immunology which I had travelling between Dublin and Wexford with Cliona "The Gaffer" O'Farrelly [prev], racking our brains for a bettaphor was a frequent theme. Anything which involves war and fighting is such a Boy Thing. It is no surprise that the Arms Race became embedded in the immunological zeitgeist during the Cold War between The West and The Reds. Think of Nixon's War of Cancer [1971] or the fake news, propagated in 1985 by the KGB, that HIV/AIDS was deliberately developed by the US as a bioweapon. The [Wuhan Chinese Virus Lab Release] biter bit, indeed.

Metaphors matter because they set an implicit agenda and channel Ways of Seeing problems and their solutions. The Arms Race has squandered our capital with broad spectrum "kill them all" anti-biotics, futile end-of-life treatments and fabulously expensive treatments for degenerative genetic diseases [Orkambi agianst CF or most recently Zolgensma against SMA spinal muscular atrophy]. Zolgensma is going head-to-head with Spinraza which I had digs at 2 years ago. Let's step away from those war-like mental formations and think rather about dance. Or Aikido, where to turn your opponent's energy away from destruction and into a neutral space. This is to acknowledge that the average microbe is either irrelevant, harmless or even benefical to human health. Using a nuclear coal-hammer to squash a gnat is noisy, inefficient and unsustainable. Turning pathogens aside through better diet >!prebiotics!<, better sunlight, better exercise, better sleep may be cheaper and less damaging in the long run.

28 + 47

 Team Tim Harford's [multiprev] BBC R4 programme More or Less is back on air. Dau.II is a slightly bigger groupie for this Polish Your Crap-detector prog than me: insofar as she told me about the new season rather than the other way around. I gave her The Undercover Economist for her b.day last year and she returned How to Make the World Add Up for Christmas. Both books are excellent: they make you think. For us, this extrapolates; from the quirky examples that float through Harford's mind to think critically about the numbers that surface in ours. That's important, if you have a feeling for numbers [Landmark Numbers for example] then you are less likely to get flim-flammed or bamboozled by the black hats lurking out there to take advantage or innumeracy.

Calculators came on the scene in the mid-70s before that adding numbers had to be done with pencil and paper. But it could be done in your head if your pencil broke. In 1983, my colleague Rob Harper could accurately tally up long columns of figures quicker than they could be keyed in to a calculator. I think he'd worked as a child in the family corner-shop. It would a rare student from The Institute in the 2010s who do that; their instinct, even for simple sums like (28 + 47) would be to reach for a calculator - or their phone. And absolutely believe the answer generated, even if bonkers.

In the 02Jun21 episode of More or Less they summarized the results of a crowd-sourced problem: "How do you add 28 + 47?". There is no correct way but you might pause and reflect on how you do this task in your head.

- * - * - * -

1. The brute force as if I had a pencil and paper approach is to add the units 8 + 7 =15; then add the tens 20 + 40 = 60; then add 60 + 15 to get 75. If your method didn't get that answer, then you might try this.
2. A number of people rounded up 28 to 30 and/or 47 to 50 and then subtracted the surplus from 30 + 50 = 80
3. Harford stripped the 7 from 47 and added that to 28 to make 35 and added that to the stripped 40. He was delighted to be told by the elementary math teacher that this was called partitioning.
4. Teacher also mentioned the idea of Number Bonds To Ten which are still taught in primary school. If you can internalise these pairs of numbers (3 + 7) (4 + 6) etc. which sum to ten, it will greatly help your mental arith. If you have small children this can be trained in by playing Tens Solitaire where you lay out 12 cards on the table and are allowed, by dealing from the remaining cards, to cover pairs of cards which bond to 10. You finish with only face [JQK or even VDR] cards visible.

I like that story a lot. It shows that there are [usually?] more ways of skinning a cat than drowning it in cream.  It pays if elementary school teachers are not too rigid in teaching methods [not only math: think phonics and other ways of teaching reading / literacy]. I suspect that some young minds will be more receptive to particular methods than others: and if provided with choice they'll get a better fit for what works.

Axolotl

 It's four months since I brought a bucket of frogspawn + mud + moss + grass-clumps down to the garden and installed them in 40 lt plastic crates. By 1st March, they had hatched into tadpoles and since then they have been wriggling around: so they aren't dead yet. But they aren't frogs neither. The weather has been scatty and unpredictable this Spring with long dry spells; several of the original puddles in the woods have dried up taking the unfortunate tadpoles to oblivion . . . but providing nourishment for the other inhabitants of the forest But (I checked last Thursday morning) there are still puddles in the same place up in the forest.

Dau.II was visiting in May and spent a bit of time observing the captive tadpoles, claiming that at least one had two back legs. This has the ring of truth because back legs appear before front, at least for Irish frogs. But I couldn't replicate this finding despite scooping several glassfuls of tea-coloured water and inspecting the inhabitants. Suffice to say, I am concerned that there will be no metamorphosis into the adult form. But a few days ago I had an insight which I hammered into a hypothesis and carried out an experiment. Anyone can have an insight, but it helps if you have several threads in your head to increase the likelihood that they will tangle into a skein from which a metaphorical ideas-jumper may be knit.

In the back of my mind is the 'fact' that our farmlet, along with most of the farms on granite bedrock hereabouts, is deficient in Selenium. We and our sheep don't need buckets of Selenium - indeed it is toxic in excess - but we need enough. Then there was my book-l'arning about amphibian development; in particular the peculiar life-status of the axolotl Ambystoma mexicanum, a neotenous salamander which comes to maturity still having gills instead of replacing them with lungs as the legs develop. Neotenous means 'retaining baby features'. Humans, as a species, are neotenous: our adult skulls look far more babyish than baboon skulls [pic]. Axolotls are on the very edge of extinction in the Mexican wild but there are numerous lines in labs, aquariums and pet shops. Axolotls fail to metamorphose into salamanders because they have a mutation which prevents them from producing TSH thyroid stimulating hormone. Without TSH, there is no thyroxine, and without thyroxine there is no metamorphosis. Having acquired a mutation which might mean the end of the line for Team Axolotl, there was considerable evolutionary pressure to make other changes. These changes included bringing on the development of gonads in a thyroxine-independent way. And that genetic solution worked until Mexico City polluted all the lakes in which axolotls normally live.

I've had occasion to teach thyroxine in my endeavours to present the Joy of Human Physiology. Thyroxine is the 'metabolic hormone': ginning up a whole host of other activities so that we work efficiently. It is peculiar in that this hormone incorporates iodine into its functional structure. Iodine, like selenium, is thus an essential micro-nutrient and if you can't get enough you're in trouble. Goitre, Derbyshire Neck, is one manifestation of iodine deficiency in the diet. Iodine also made the news 20 years ago, when The Man delivered anti-Chernobyl.II tablets to every household in Ireland.

My hypothesis developed as the idea that 'my' tadpoles were slow to embrace adult life because they were iodine deficient. Last week therefore, I got my ex-colleague A to score me 30g of potassium iodide KI which I made into an aqueous solution and added to my two amphibian ponds. The molecular weight of KI is 166, so 166g of KI dissolved in 1 lt of water gives a 1 molar solution [mole prev] which contains 6.022 x 10^23 molecules of iodine.  I dissolved ~16.6g [tenth of a mole] in water before adding it to two 40 lt containers; so there are only 6.022 x 10^22 or 6,022,000,000,000,000,000,000 iodine molecules to share among a couple of hundred surviving tadpoles. Should be enough.

B Day

 D-Day 6th June 1944 is long long ago. I've had two Sundays off, but I really need to clear the backlog of this is could interesting links

• Chop-chop
• Farming snails for food [as R]
• Dip-netting salmon for food
• Tapping trees for food
• Food irrelevant to judge's judgement
• Soul food makes everyone happy
• Farms with trees are better
• Trees? Bonny Portmore ♬ ♫ ♩ ♪
• Trees? Shinrin'yuko 森林浴 = Forest bathing
• Japan? 4th Grade
• Flotsam = Lego
• Tom Scott? James Lovelock, hamsters and microwaves.
• Never Seen: minority interest collection of the UK Science Museum
• Oroville 2017 [prevs] Grady the Engineer's retrospective
• Erosion? Rock trundling it's a thang
• Rocks? Split them with plug'n'feathers
• Engineers? building tooth-pick structures for earthquake zones
• Fakkin' frakking: a river on fire
• The End . . . of A River Runs Thru It. I am haunted by waters.

Reichenback

Jaysus, I'm wringin', me finger-nail is broke and I could murder a cup of tea. On 22nd May, my writer-persona, quite casually, pitched The Blob off the cliff announcing with puerile melodrama <ta-DAH> that, after eight years of daily posts, it was The End. A handful, maybe two handsful, of my regular readers wrote in or commented to say So long and thanks for all the fish. That response was considerably more measured than the hysterical fan-boy storm-cup that Conan Doyle generated when he made Sherlock Holmes take one for the team by heaving self-and-nemesis into a fatal encounter with the Reichenbach Falls [as L, hat goes first].

Conan Doyle was, at that stage, really tired of his know-it-all detective. He had other literary fish to fry and Sherlock was a massive distraction. "I must save my mind for better things, even if it means I must bury my pocketbook with him." His two volumes of Napoleonic War Brigadier Gerard stories are really good fun and the period details are exactingly researched. Delving further back, The White Company is a ripping yarn about mercenaries in the 100 Years' War. I probably have it confused in my head with Walter Scott's Quentin Durward which is also set in France, although 100 years later. One of the reasons for Conan Doyle's enduring fame is that all his books are readable. Anyway, the poor fellow was surprised at how invested his readers were in Sherlock Holmes and, after a holiday from the relentless treadmill of producing 'tec thrillers, he wrote The Hound of the Baskervilles. HoB was set chronologically before Reichenbach, but The Adventure of the Empty House brought Holmes back from the dead and the carou$el $tarted grinding the corn again. Holmes had climbed up and down the cliff beside the Reichenbach Falls to evade the dastardly rock-pelting confederates of Professor Moriarty and escape. Moriarty was defo dead, though.

But enough of the famous and the dead, this is about meeeeee. Wet but unbroken, I've crawled back up the precipice and beg your attention: I am hereby giving notice that The Blob is back on a when the spirit is upon me basis. Apart from anything else, it's useful as a record of the everyday story of country folk. The really dramatic events like the DarwinDay storm are in the public record; who did what with which sheep, not so much.