Wednesday 27 March 2024

Pratchett Remembered

TERRY PRATCHETT a life with Footnotes* by Rob Wilkins

*The Official Biography appeared [Go Libraries!], all 400 pages of it, in our living room a few days ago. Reader, I read it. I didn't need to do this, I didn't even really want to do this but I started and so ploughed on to the end. Which is more that I can say for at least two of Pratchett's Discworld books. The picture [L] shows Jocelyn Bell-Burnell [bloboprev], David Attenborough and Terry Pratchett in medieval kit receiving honorary degrees from my alma mater TCD.

Rob Wilkins, the biographer, was the long-term PA / secretary / amanuensis of the prolific and commercially successful author Terry Pratchett. He dead, so fans are not going to get anything more out of him. But Narrativia aka Terry Pratchett Inc is still in business with spin-offs. Merch here. This biography is another spin-off, I guess. It is very much the hagiography, because Wilkins is still working for the Pratchetts at Narrativia and I think still using the Pratchett Estate as his office. A biographer could lean hard into the disagreeable, anger-management=poor, controlling aspects of Pratchett's character; could be more critical out the make-weight elements of the Canon; could be bothered to include an index.

But then few of the people who are going to read, let alone buy, the book are going to want those details. I'm ambivalent about the works of Pratchett. I am close enough in birthplace [180km] and birthdate [8 years] to recognise the allusions in the Discworld satires but that's not enough to retain my interest. If I had wanted to be in the English Media Gang, I coulda been a contender: but I didn't and I left the country before Terry Pratchett started writing novels. And I still get most of the in-jokes. You can take the boy out of the country but you can't take the country out of the boy, I guess.

The most interesting bit of the book is when Pratchett was at the height of his commercial success and before he got his adverse mental health diagnosis in 2007. That's when the author stopped being a knowing, driven, sole-trader with a gift for words; writing because he can do no other. The commercial publishing world has agents, editors, translators, cover-designers, type-setters, printers, and booksellers. This memoir documents how most of the people in this trade (as in science, teaching or probably any other 'industry') are teetering at the edge of their competence and incapable of thinking outside a paper-bag let alone Outside The Box. A number of laughable errors of taste, failures of empathy or business sense are documented by Wilkins. Like expecting Pratchett the golden goose to work a 5 hours book-signing session without providing a decent chair, a table with four legs the same length or even a curling sandwich.

Nevertheless, a minority of workers in this corner of the book trade are really really good at their jobs. Wilkins, and some of the book-dedicatees in the Canon, acknowledge that good editors make a great book. Good publicists have to do more than lay the latest book before the eyes of people who count (money). And never forget that luck and timing still play their part.

Monday 25 March 2024

Bigging up the Danes

For my sins, from 2013 to 2020 inclusive, I taught Human Physiology to 1st year Pharm tech students. My only qualifications for doing this were a) I have a body b) nobody else wanted to do it. I inherited a bunch of PPT slides, the Learning Outcomes and 30-something students almost all of whom were women. Don't know about the students, but I learned a lot. Human Phys is all about homeostasis - keeping the various systems of the body in trim to quite fine tolerances. You know this: over-heating by even 1 or 2 °C makes you feel like crap. If your blood pressure goes up a little, you're likely to blow an aneurism or have a stroke . . . goes down a little and the blood will rush from your head and you'll collapse to the floor. Your bod keeps to the set-points of tolerance with a complex system of checks & balances = belt & braces = redundancy. My fave hormone Vasopressin squeezes the smooth muscle AND reduces water-loss in the kidneys both effects geeing up the blood pressure.

I put it to you that 9/10 people stopped on the street will have heard of insulin and have some idea about what it does [regulates circulating blood sugar). otoh those same 9/10 will nope out when asked about glucagon. But you absolutely need them both and the receptors to which they bind to effect their magic on each cell of the body. I've shared my discoveries about glucagon several times in The Blob. TIL that, like a lot of proteins /peptides, the hormone glucagon is derived from a rather larger "pro"-peptide which is 180 amino acids in length. After translation this longer protein is enzymatically cleaved into three quite similar peptides, at least two of which are biochemically active: a) glucagon b) GLP-1 = glucagon-like peptide #1 and b) GLP-2. This shows that three copies of the active bit 'were created' in evolutionary time and have subsequently been free to mutate and acquire a wider range of specific functions.

GLUC      ------HSQGTFTSDYSKYLDSRRAQDFVQWLMNT----
GLP1      HDEFERHAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG--
OZEM            HxEGTFTSDVSSYLEGQAAxDFIAWLVRGRG
GLP2      ------HADGSFSDEMNTILDNLAARDFINWLIQTKITD
*::*:*:.: .. *:. *::*: **:: 

These peptide hormones are at nothing unless and until they dock with a specific receptor sitting in the membrane of all the cells in the body. GLP1 binds to <surprise!> the GLP1 receptor which starts a cascade of internal reactions to do with glucose metabolism. These reactions may be wide-ranging in different tissues (as with vasopressin == ADH anti-diuretic hormone two paragraphs up). One known effect is the inhibition of glucagon. That will prevent free glucose circulating which means that insulin won't have to work so hard to keep glucose levels at their set point. and that would be good for diabetics. A few years ago boffins looked at the sequence of GLP1 and thought "target". They modified the sequence of GLP1 [see alignment of the amino acids in colour above] to create semaglutide which really binds the GLP1-receptor.

Novo Nordisk the Danish Megapharm which owns the IP on Semaglutide = Ozempic = Wegovy is now the biggest corporation in the EU with a market cap of $500 billion. Ozempic is the company's golden goose and is responsible for pretty much all of Denmark's economic growth during Coronarama. If you'd bought shares in Novo Nordisk  5 years ago you would have had a 5x return on your investment. Ozemic featured on RTE on 4th March b/c World Obesity Day.

Ozempic hopped through all the regulatory hoops as an effective treatment for type-II (late-onset) diabetes because of it's domino effect on the regulation of blood-sugar levels. Later on it was realised that Ozempic was effective in helping ppl with obesity shed a few kilos. It was therefore widely prescribed for that condition. In 2021, the FDA approved this use of semaglutide, under the trade-name Wegovy. 

It turns out that Novo Nordisk, even with outsourcing production to several other facilities, cannot produce enough Ozempic to satisfy the market in diabetes and obesity. Part of the problem is that this drug is being widely prescribed 'off-label' to reasonably healthy people who desire to trim their midriff to look good [and maybe pull their cousin's BFF]? at an up-coming family wedding. That's how markets work: well rich people can obtain a scarce resource - because money - and can insulate their conscience from the effect this choice has on really sick poor people on the other side of the tracks. And social media influencers? They can eat their own brittle!


Sunday 24 March 2024

Close encounters

Whaaaa's happenin'?

Friday 22 March 2024

Wexford Roadeo

Oy vey, my son the Engineer designs signalling systems for railways in England. Railways generally get a green pass. Their rights-of-way were acquired in the 19thC when Capital was king. In general railway stations are plunk in the centre of town, so it's still quicker to travel between major UK hubs by rail than by flying. Because the last 10km in from the airport is shared by too many cars, buses, traffic lights and potholes.

An Bord Pleanála ABP is a powerful quango, the last court of appeal in Irish planning. They can take a hella long time to come to their considered opinions about whether projects can go ahead. There is plenty of scope for corruption and their deputy chair just avoided getting banged up in chokey for losing count of how many cunning schemes in property development he had going on the side. otoh, someone has to ensure that major infra-structural projects are compliant with multi-faceted rules, regulations, guidelines, plans and laws. I wouldn't trust engineers, or politicians, or me, on their own [each with their own limits, bias, obsessions] to decide where new roads should go . . . even if "we" agree that new roads are really what people or planet need in the mid-21stC. There are so many more stake-holders than 19thC railway engineers encountered: 

  • Population and human health
  • Ecology & biodiversity
  • Soils & geology
  • Hydrogeology & water
  • Landscape & visual
  • Noise & vibration
  • Air quality and climate
  • Archaeology & heritage
  • Agricultural land
  • Other land assets
The rights of these stake-holders are vindicated by ever-shifting regulatory paperwork published by county, country and the EU.

March is when Engineer's Week happens. Wexford Science Café were induced to Ask An Engineer for their March meeting. I suggested an evening on new roads projects in the County. Our convenor ran an engineer to ground. On 19 Mar 24, Bratislav Dimitrijevic, unburdened himself about the many and varied tasks he had to do as Project Manager, N11/N25 Wexford by-pass. When he graduated in Serbia 20 years ago, he little imagined that in 2023 he'd be haggling with an Irish farmer about a cattle-pass under a proposed road in Wexford. Which proposed road? 75 different routes for the 33km between Oilgate (end of the M11) and Rosslare EuroPort have been considered over the last 5 years. Here are the main options:

In April 2023 the "final" route was chosen after optimizing all the variables. It's more-or-less Route C except that the final route is going to use the existing right-of-way along the Wexford Bypass and ?upgrade the roundabouts? The Green Agenda requires the project to include Park&Ride facilities and "active travel" options: we should be able to walk/cycle from Oilgate to Rosslare barrier-separated from cars and trucks. At the WexSciCaf meeting on 19/Mar we were shown The Map with a fat yellow line looooping across it. This 300m wide corridor has been "sterilized" for planning purposes. But the final road will be only 20m (on the level) to 50m (cuttings and embankments) wide. Apparently ~380 land-owners (great and small) have stake in the 300m x 33,000m strip.

The River Slaney at Ferrycarrig has foreshore and tidal slobs which make it a SAC Special Area of Conservation. 13,500 sq. km. of this our Republic (including 3 stream-fronting hectares at Chateau Blob) are so designated: that's 18% of the whole country. The new bridge will be parallel to and West of the existing 1980 bridge. Built before SACs were a twinkle in an ecologist's eye, this bridge is 125m long and supported on 7 concrete piers sunk in the tideway and damn the otters. Check out the Old Ferrycarrig bridge. The new bridge won't be allowed to drip diesel-contaminated rain-water into the holy Slaney valley, let alone sink concrete piles into the slobs. The engineers are accordingly looking at building another 800m bridge to facilitate trucks and tourists spreading out across the country having arrive at Europort Rosslare. The RoseFitzKenn bridge over the R. Barrow 40km to the West is 890m long with the longest span 230m.

My question was whether sterilized land-owners who were not finally CPOed (compulsory purchase order) would be compensated for spending ?5 years in legal and asset-management limbo. I didn't get an answer to that. But we were invited to reflect on the plight of land-owners abutting the corridor: they get nothing except noise, disruption and envy.

Wednesday 20 March 2024

Trigon Empire

I do a lorra ear-books though Borrowbox. Sometimes I 🐸wish🐸 that a chunky book on my reading list was available in the audio medium but I don't go all into a rage about it; I just question why completely unsuitable books are rendered into .mp3 instead. Like who was thinking what when they published How to Draw a Map in audio . . . with no maps?

Rachel Riley [R] makes arithmetic look easy. Because, for her (and me), tricking about with numbers is easy. It's partly mind-set and aptitude but also partly training. Old style National School rote learning emphasized the training. Thus you get generational transfer of times-tables and arithmetical tools transmitted by national school teachers who were good enough at the tricks but really had not the bog's notion of the under-lying principles and no particular feeling for numbers. A bit like me being required to teach 2nd year college Physics when I'd failed my Physics "O" level at 15

I was in a pretty funny situation earlier in the month ear-booking through At Sixes and Sevens: How to Understand Numbers and Make Maths Easy by Rachel "Countdown" Riley. Obvs [hint: audiobook] without pictures. I hear Riley brightly uttering some bafflegab "a cubed plus b cubed all in brackets is not the same as a to the half plus two sin theta plus b raised to next tuesday" and adding confidently "it will all be clear if you refer to the triangle on page 14 of your PDF". Hint: there is no PDF b/c Borrowbox don't think it's important.

The ostensible reason for the book is for parents to help their kids with the math which the youngsters are being cold-bath-after-breakfasted at school. The first tuthree chapters are on-message and quite inspiring. Asserting that math anxiety is a state of mind and that we all (particularly grrls) should stop labelling ourselves (or anyone else!) as crap-at-math. But soon enough the Riley accepts the school math curriculum at face value and offers a number of different ways-of-seeing to help us crack the code. Which is fair enough given the Mission Statement for parents to help their kids with the math

But really? wtf are schools putting everyone through simultaneous equations? Puzzles which can be solved using SimEqs have been around for about 2,000 years and they currently get binned in the Algebra chapter of maths text-books. But that's it, they are puzzles. Riley professes to love fractions, cats and algebra and handles SimEqs by presenting a plainly out-of-reality but mildly amusing conundrum. The puzzle involves mix and matching school dinners where the menu offers rice, salad and tacos and various combos of kids who come back home with receipts for the cost of their dinner. In this fantasy land The Parent says "Let's work out what the cost of each item is". Because the price is bafflingly not on the menu? Ah ha, this is why the kids are comen como mexicanos it's because
R + S + T = alphabetical algebra.

1r + 1s + 2t = £10.00
3s + 2t      = £10.00
2s + 3t      = £14.50

There follows 5 minutes of ". . . we can now plug r = 2s into either the second or the third equation . . ." which may be clear as a blut of chili sauce IF you have the PDF but in audio-only it's just so much word salad. I like these sorts of puzzles; I'm okay at solving them; but it's a long way from a justification for requiring mastery of SimEqs for all teenagers in school because it will set them up for real life. Because in real life (if you-the-parent really needed to know the cost of a portion of salad at school) you'd send young Jimmy in with a note for the dinner ladies "Please tell my poor Dad how much the salad costs [£__.__]"

I had At Sixes and Sevens in my ears for 8 hours as I fossicked about doing outdoor chores. The last 2/3 of that time, absent the PDF, it was a warm bath of familiar nonsense - like overhearing two people talking Portuguese behind me on a bus. In 1984, my Portuguese was fluent enough to read a newspaper and get what I needed from people in shops and offices; now not so much - but hearing it again triggers happy saudades.

But 'ere: I did learn something which has been hidden from me in plain sight for all my mathy life. Trigonometry is all about the -metry of Trigons aka triangles in mathogreek . . . pentagon, hexagon etc. Trigan Empire in the title is a nostalgic reference to a 1960s childhood getting the glossy mag Look and Learn in the regular. Every issue had a two page spread following the dynastic antics of folks who dressed like Romans and carried swords but also had anti-grav space-ships and phasers. It was great!

Ans: rice £2.00; salad £1.00; taco £3.50

Monday 18 March 2024

Endo dont cogn disson

Years ago, when  we lived in England we were tickled listening to a commonplace report on the BBC. It was about the non-Pitman shorthand used by ?orthopedic surgeons? to record patient injuries and treatment. "lvd scr from kn to hp" [livid scar from knee to hip] was absorbed into family lore; along with scenes (of course he's the F*king Farmer) from Withnail and I and baguettes from Beineix's Diva. 

I was reminded of this because we have, perforce [retirement], enrolled with a new dentist. Word to the wise: choose a dentist at least 20 years younger than you are: having them die on you is extremely inconvenient. Dentistry has moved on tremendously in my 60+ years of tooth care. No anaesthetics in the early 60s; the drills turned by wire drive-trains. When you change dentist for a younger model, it's like skipping 30 years of technological improvement. The new dentist has a screen on the ceiling to entertain clients as he digs into their buccal cavity. There is a whole new set of acronyms and jargon to wash over the mind as he dictates his assessments to the dental tech. There is presumably enough detail that the status can be recorded and recalled in six months' time. Half a year being the standard time-counting unit in dentistry.

Initial visit in August 2023 allowed introductions to be made and there was time to do one bit of remedial work on lower left six: the front-most molar. There is a crack which extended an undetermined depth into the roots and which may burst asunder at any moment. New Dentist (N.D.) tidied up the long-existing, multiply-patched cavity with that new-fangled UV-setting ceramic filler but added some bondo glue into the mortar in a probably vain attempt to keep the two side of the crack in contact. "That will do for now, come back in 6 months and we'll see how/if anything has shifted". In Feb 2024, 183 days later, I was back in the chair having another X-ray to monitor progress. "that tooth probably needs a crown to hold the two sides together; it would be better to sort out the foundations first - because doing a root-canal job through a crown is no laughing matter; I'm going to refer you to the Endodontist down the street". 

According, a month later I had an early-day appt with the said Endodontist. Once upon a time, a dentist was a strong fellow with pliers; now the profession is fragmented into sub-specialties. "Dentists" do filling above the gum-line; "Endodonts" plumb the depths. Dental surgeons do extractions, bone and gum work. 

I got into a 'discussion' with the Endodental Tech about where to park. If I parked on the street, I was likely to run out of time and get a hefty ticket. whereas if I parked somewhere else then I'd get the full three hours of a typical Endo-session and save €2. I explained that 5 years ago, I'd really have engaged with that sort of tightwad penny-pinching but since retirement my business model was much more support the economy and can't take it with you

The cognitive dissonance came in when the Endoboss outlined the likely course-and-cost of treatment. 

  • a referrer's referral to an Endodontist in another town who owned a 3-D Xray machine [€180]
  • 3-D informed re-scrutiny of the path of the, rather occluded, root canals [€100]
    • these machines are the latest thing and only available in Ireland for the last tuthree years; the pictures are really informative
  • three hours drilling down the 3 roots of the one tooth [€900 if progress straight-forward, more if the procedure required two sessions]
    • cleaning, bleaching and filling the drilled cavity [€0 - fitted as standard]
  • returning to my above-gum dentist for the crown [€X indeterminate amount]

All this delivered with a grating, hand-wringing apology for how much it was all going to cost . . . with no certainty that the outcome would be a long term solution to the goddam crack in my aged molar. The cost sounded reasonable considering how we're in the market for a new sofa. But it was super-weird, while on the same dental couch, to be haggling over €2 with one member of the Endo-practice and €2,000 with another.

The alternative: hope that there are no stones in the lentils and keep using the existing kludge on lower left six until its rift rifts and then have it taken out [€180]. Apart from the money, getting a crown or a dental implant is a different matter for an ould chap in his 70th year compared to our 20-, 30- and 40-something offspring.

Sunday 17 March 2024

St Patrick's Day 2024

Lá Feile Padraig, I hope you have your feet up.