Sunday, 18 June 2017

The Dadical

Dadical is a new coinage, as far as my daughters are concerned, having been applied to me yesterday. 'Popsicle' would have been possible except that it is already a word for something cool and refreshing: hardly applicable to The Da. Back in  April, Dau.I and I went on the March for Science in Dublin. The agreement was that she'd come out For Science if I would come out for The Gays. That was tentatively fixed as having a date with the Dublin Pride March on 24th June 2017. But 2 months is a long time in radical politics and I washed up in Cork this weekend because a) it was my birthday yesterday b) therefore Dau.II had bought us tickets for ProdiJig, a hoofer troop of which she is a fan. Here we are, Dau.I and her Dadical [Left for Rights! close-up below] wearing identical repealthe8th badges.
Because good things always come in threes, it turned out that Dau.I could get her pay-back and we could have a family outing round Cork city centre, by going on the local Repeal the Eighth rally, which kicked off at 1330hrs yesterday. Here  I explained the issues about the 8th Amemndment to the Constitution back in March. With two daughters in the 20s, I get to hear about those issues from the horse's mouth as one might say. A case could be made, and the girls are quite keen to make it, that only women of child-bearing age have a locus standi on the matter and they invite nuns, grannies and blokes of any age to just hold their whisht about the rights and wrongs of abortion. My late lamented, and rarely PC boss had a phrase "your rights end where my nose begins" which I am inclined to take up on his behalf. That's  a trip-off-the tongue way of articulating an overarching tolerance of diversity. Matter-a-damn what you do at home - eat pray or love whomever or whatever you wanted because it was none of my business. It's not a literal nose as the boundary - mowing the lawn or raising cain at 0300hrs on a week-night is not tolerable unless your neighbours all have ear-plugs.

One problem with Rights is deciding who is to vindicate them. I don't think that normal people would have much tolerance for a return to trial by combat in which the strongest, fastest or wiliest fighter was demmed to have found favour with the deity. We still haven't cracked the closely related problem of trial by lawyers because it is clear statistically that the richest person wins disputes a disproportionate amount of the time. It is more or less a sham to appoint a lawyer to fight for the dispossessed because they are hobbled by lack of money.  ANNyway the effect of the 8th Amendment as it has come to be interpreted is that the right to life of the unborn trumps pretty much any right of the mother except avoidance of her death. The vindication of this right has led to one high profile case, Savita Halappanavar's, which killed both mother and child and that doesn't seem to be the best possible outcome by an objective assessment. The right to life was brought into focus again in 2015 when a woman, 17 weeks pregnant was kept on life-support after sustaining a catastrophic internal blood clot that left her brain-dead.  The Hippocratic Oath is specifically against abortion but we don't need to adopt wholesale the ethics of ancient Greeks whose civilisation had a foundation of slavery in the silver mines of Athens. We could move to the 19thC with Arthur Clough's verse advice "Thou shalt not kill / But need’st not strive / Officiously, to keep alive." which I've trotted out before on end-of-life issues.

Here's the thing, right now we are in an 'every sperm life is sacred' era: caught between a life is cheap time when a child could be hanged for stealing a handerkerchief and an uncertain future. The trouble with Rights is when they are prefaced by a starement like "We hold these truths to be self-evident . . .".  To which the skeptical reply is Whoa! no we don't. Rights that were obvious to all thinking people at some time in the past are now considered repugnant to many. The rights of the unborn are a super-polarising concept about which it is hard to have a rational discussion. Discussion degenerates into a recital of anecdotes (I gave two, Savita H and life-support,, in the prev para); young women fall pregnant for all sorts of reasons and travel to the UK for a termination - at a rate of 10-30 every day so they already have the ability to safely become unpregnant. If The Patriarchy would just shut up, this Irish Right could be vindicated in an Irish clinic. Another place to start the discussion might be to suggest that we throw out the Absolutes - because we don't give an unqualified right to life to Syrian refugees, or starvelings in the Sahel or Somali pirates. We now live in a 21stC where 7.5 billion people are eating their seed-corn and despoiling the planet. Fewer people please: coral reefs, rain-forests and every species on the IUCN red list have rights as well as every person or proto-person on the planet.

Techno Sunday 180617

A few bits on technological solutions to making things.

Saturday, 17 June 2017

Use it or lose it

Can you hold a pencil? Although not recognised as such by the Transportation Security Adminsitration, pencils can be used as a lethal weapon, if hexagonal they can also be used when there are no dice available, or to fish termites out of a hole for dinner. Chimpanzees could carry out any of those tasks but only humans can use a pencil to write their name . . . or The Grapes of Wrath. That's because we can use our thumb, index and middle finger in a 'power-precision grip' PPG and manipulate the pencil to make marks of tiny precision and delicacy - not only writing but drawings, graphs and diagrams that accurately convey and record meaning. Some drawings are so realistic that you wonder why the perp didn't use a camera. The PPG isn't only used for pencils but for lifting jam-jars, bullets, day-old chicks and baseballs. It is hard to program a robot's computer to pick up an egg without crushing but your muscle and mind achieve this without a conscious thought. It takes time to get these tasks right, babies are clumsy, can't get the spoon into their mouths and make a sloppy mess all round them until they learn how. Letting Petal feed herself is a long haul strategy but it pays dividends. Baby led feeding, adopted by The Boy and his family, saves a mort of money because the kids pick over the family dinner rather than being catered for with Gerber Glop, Materna milk puddings or Cow&Gate creamed rice. But BLF also drives the development of the mind, autonomy and a sense of self.

One of the things that neurologists are discovering is that the doors of perception need to be opened and closed, and frequently oiled, if they are to develop and retain utility. The brain is plastic and there are many potential calls on a neuron. After a stroke, you may laboriously recover the use of your limbs and the power of speech by re-purposing and recruiting other neurons to filfill the functions ablated by the ischemic event.  If you are born without eyeballs then the part of your brain destined to become your visual cortex is effectively snapped up by other functions and put to good use. This is an argument for embracing hearing-aids - to stop the auditory cortex closing shop altogether.  If you don't use your hands to carry out finely dextrous tasks then your don't get to keep the motor neurons and that may have negative impact on your general cognitive development.

When I was growing up we played with wooden cotton reels, saucepan lids and sticks, It was like reading the book rather than watching the film of the book. Our imagination filled in the bits between saucepan lid and shield; between Lego and Bridge of the River Kwai; between a plastic airplane and Dresden Valentine's Day 1945. Children then lived in their heads and could subvert efforts to make them play in particular ways - as exposed by Saki's story The Toys of Peace. The youth of today have no patience with wooden blocks or cardboard boxes because they have Lara Croft [bloboprev] to steer through somebody else's imagination.  David Gaul and his boss Johann Issartel at Dublin City University have got some data [PMID 26735589] on how the modern world may be turning the digital generation into blobs unable to zip up their own coats or pick their own noses because the only fine motor skill FMS they can carry out is a swipe or a tap.
Next time you see someone tying the shoe-laces just look at the task sequence required: it's a wonder that we can carry it off at all and I know my twin sister had to do this for me when we first went to primary school. Gaul and Issartel measured 250 kids divided between 2nd, 4th and 6th classes = aged 7, 9 and 11 and found that they got better at a standard set of motor coordination tasks as they grew up. That's good, you'd hope the young shavers were learning something over those 5 years.
Key: fine motor precision (FMP), fine motor integration (FMI), manual dexterity (MD) and upper-limb coordination (ULC). The bars are mean and std.dev. for 2nd, 4th and 6th class. Quite a lot of variation there.  But concern developed when they compared the skills to the normal average for children of the same age:
Key: [annoyingly different from the tasks in Fig 2 above] fine manual control (FMC) and manual coordination (MC) units and Total Fine Motor Composite (TFMC). You can see that 2nd class students start off close to the average [the 50 line] but steadily fall behind 'normal' as they grow up. David Gaul was on the wireless the other day and he suggested this increasing deficit was a) disturbing and b) possibly due to the swipiness of the youngsters environment decreasing their capacity to do up a button let alone sew another one on when they oafishly rip the original one off trying to force it through the wrong button hole [I paraphrase!]. Skeptics among you will note that the error bars are all large and comfortably embrace the 50%=normal point on the standard score axis. Trouble with social science and medical experiments is that it takes yonks to gather up any kind of sample at all at all and even then it may not be statistically robust. The blue 2nd years are different people to the green 6th years and the difference in the means may be a statistical artifact. I hope that the authors aren't going to park the project having gotten this publication out because there is a longitudinal study crying out to be done: same kids tested at two year intervals. And of course, we need someone from Montpellier or Bordeaux to replicate the study in French schools. And a control set of home-educating children to see if school is sapping the will to live of the children who are ground through that inexorable mill. This reminds me of another place where the external environment impinges disastrously on neuro-musculat development - the myopia epidemic driven by the absence of sunlight.

Friday, 16 June 2017

Anti-inflammatory in the balance

Inflammation is a good thing, it is the body's response to physical and biological assault and mostly it works a treat. The other day I was yanking my boots out of the car-trunk and nicked my finger on a tooth of the chainsaw.  It didn't hurt but bled quite a bit and the hole was sore for about 24 hours. A nice clean cut; any bacteria flushed out by the blood flow; some local white blood cell activity to mop up the remaining bugs involved a little swelling, a little tenderness and a little redness. Sounds like inflammation to me - I share an old Latin mnemonic with my Hum Physiol students:
  • Calor heat
  • Dolor pain
  • Rubor redness
  • Tumor swelling
Sometimes, however, inflammation can be a disastrous over-reaction. Cholera toxin is no fun - it's a toxin after all - but the body's response to the presence of Vibrio cholerae is to flood the intestine with fluid to flush out the toxin producing bacteria: flush flush flush until the cistern and the header-tank run dry and you die of dehydration. They say that fit young people, with active inflammatory /immune systems died disproportionately during the Spanish 'flu pandemic of 1918: the treatment worked but the patient died. One of the consequences of developing an auto-immune disease - rheumatoid arthritis; multiple sclerosis; psoriasis; psoriatic arthritis; lupus; Goodpasture syndrome - is that there is tissue damage. Tissue damage means an inflammatory response which means calor dolor rubor & tumor which is a bloody nuisance and makes you feel utter crap for much of the waking day.

What if, some medical researchers asked, we could damp down the immune response. That would alleviate many of the distressing symptoms of auto-immune diseases and might even promote a bit of healing in the damaged tissue. One of the positive outcomes of 30 years of molecular biological research is that we now have model incorporating some of the key players in the inflammatory response: both what molecules are involved and what cells play a part. As with the nervous system, we reckon that the cellular response is controlled by external molecules = "ligands" which dock and bind with receptors embedded in the cell membrane. "Molecules which are produced by one cell type and act on another cell not in immediate proximity" is a definition of a hormone. But in the context of immunology and inflammation such molecules tend to be called cytokines. Each cytokine will have a particular look&feel and function and will only be effective if it makes contact with a specific receptor. Both cytokines and their receptors are proteins of which we have an inventory of about 100,000 different forms, some quite closely related to each other. Clearly there are two ways to turn inflammation down a notch or two:
  • destroy, disable or interfere with the production of one of the cytokines
  • put a spanner in the cytokine receptor to prevent docking
Stress is also A Good Thing - it is a way of keying up your physiology to deal with a problem - tiger; alpha-male; sudden change in weather; potential mate - but is ultimately damaging if it goes on for too long. Human Physiology, I intone at almost every lecture, is about the checks and balances of homeostasis. Short cartoon, reasonably on the right track. Homeostasis is maintained in the normal run of things by having both pro-inflammatory and anti-inflammatory cytokines and dribbling them out in the correct proportion for the given situation.

One way of nobbling a cytokine is to develop a 'biologic' an antibody against that molecule. I've written before about the absurd unmemorable hard-to-say names for drugs. But there are some clues: if it ends in -mab it is a monoclonal antibody developed by injecting the . . . heck I'm not going to explain this because it's w-a-a-a-a-y outside my competence so I'll hand you off to John Nguyen at Massachusetts College of Pharmacy and Health Sciences - what's a MAb and how are they made.
More etymological clues:
  • omab (original and not the best) = murine monoclonal antibody
  • ximab = chimeric (part human part mouse) monoclonal antibodies like infliximab [prev]
  • zumab = humanized (less mouse more human than ximabs)
  • mumab = fully human monoclonal antibodies are made in human cell lines skipping the mouse protocol. Try saying adalimumab with clarity and authority when explaining its potential to a worried patient.
  • Another John Nguyen gallop through a bunch of specific MAbs, their names pronounced and the uses described
The point about MAbs is that they are extremely specific; they will nobble the target molecule and leave everything else alone. So there are usually fewer side-effects. I've written about infliximab before which targets TNF-α a cytokine that cranks up the inflammatory response when cancerous cells appear.  Its name tumour necrosis factor tells the story: with TNF-α tumours are suppressed without it they grow.  Clearly TNF-α is A Good Thing because cancer is the Black Hat of modern Western medicine . . . except when it runs away with itself and cranks up inflammation when it shouldn't. This is the case for a string of auto-immune diseases including rheumatoid arthritis RA, ankylosing spondylitis, inflammatory bowel disease IBD , psoriasis, and refractory asthma and all these disorders can be treated with anti-TNF therapies.

The trouble is that although the MAb is extremely specific - it will take down TNF-α only - TNF-α is a key work-horse in maintaining homeostasis all around the body. By controlling the level of this cytokine to mitigate the debilitating effects of RA or IBD, the patient no longer has enough of the stuff to do its says-on-the-tin tumour necrosis job and lymphomas are a common side effect under long-term use of infliximab. This robbing Peter to pay Paul is a problem in many aspects of modern medicine and the good doctors spend a lot of time and money juggling the competing forces to get a drug and a dose that is a Goldiloxian just right. Cue not strictly relevant fragment of verse:
I balanced all, brought all to mind,  
The years to come seemed waste of breath,  
A waste of breath the years behind
In balance with this life, this death.

Thursday, 15 June 2017

La Joconde

It's someone's birthday today and the triptych above gives a clue as to who deserves a roaring conflagration of 538 candles on her cake. I'm sorry, if there are any youthful readers of The Blob, but this woman has more likes than young-wans Taylor Swift, Adele and  Ariana Grande put together. I have here cast her in a heroic role to show how far her picture can deviate from 'the truth' and still be recognisable. I don't think a satirical pastiche of Ariana Grande as Miss Piggy would work; not least because half the kids who sing along with AG because they know all the words would not recognise a cultural icon of a previous generation - how quickly they forget.

ANNyway, Lisa di Antonmaria Gherardini was born in Firenze on 15th June 1479. She never got to taste Firenze's famous Sou'wester Cake because that's from another time . . . and another place. But the consensus is that she lived a longish and happy life; hence the enigmatic smile. She married, at 15!, a cloth-merchant in Firenze called Francesco di Bartolomeo di Zanobi del Giocondo, was comfortable financially and had six children (one daughter died young) and passed away, in the fullness of her years (for those days! next week I'll be the same age as she died and I'm not quite ready to go yet) in July 1542. Her, now mega-famous, portrait was begun by Leonardo da Vinci in 1503, when she was in her 20s and convincingly matronly and content - if you believe the smile.  The painting is, as everbode kno, now behind bullet-proof glass in the Louvre in Paris. Of the 10 million people who visit the Louvre each year, 80% of them are poured out of tour-buses so that they can tick the been-there-done-that box in their itinerary.  That's 20,000 people a day trooping past and ignoring the amazing treasures that are in other rooms of the old royal palace. The folks back home in Kyoto, after all, think that the Nike of Samothrace is a brand of shoe. Why not listen to Emma Durrant talking about something Louvrelse in her best Dublinese.

The portrait, although commissioned by the Giocondo family, was whisked away by da Vinci who continued to work on it for another ten years in Italy and France and I don't think it ever got to hang in the Giocondo's hallway. Accordingly, knowledge of its provenance was lost and speculation grew legs.  Many famous women were seriously suggested as being the model: Isabella d'Aragona,Cecilia Gallerani, Costanza d'Avalos, Isabella d'Este, Pacifica Brandano, Isabela Gualanda, Caterina Sforza. There is even supposition that the actual sitter was Leonardo himself in his pre-beard days, or his impish assistant Salái. The latter claim is vigorously disputed by the suits at the Louvre.
In 2005, Armin Schlechter, a scholar blowing dust off the antient folios in the archives of Heidelberg U discovered a marginal note in a copy of Cicero's Letters written in 1503 by Agostino Vespucci. Seeing the painter Appeles referred to by Cicero, Vespucci wrote in ink "Apelles pictor. Ita Leonardus Vincius facit in omnibus suis picturis, ut enim caput Lise del Giocondo et Anne matris virginis. Videbimus, quid faciet de aula magni consilii, de qua re convenit iam cum vexillifero. 1503 octobris" [Translation]. Scribble scribble Mr Vespucci tsk! That sort of thing may well remind you of  the most famous marginalia Hanc marginis exiguitas non caperet written by Fermat and serving as a challenge to Mathematicians for the next 350 years. Incidentally Agostino was cousin and contemporary of Amerigo Vespucci whose name was attached to the New World over much stronger claims by other explorers.

Wednesday, 14 June 2017

Mental load

As you know, if you've been here before, I surf a corner of the blogosphere which starts at 8-10 jumping off points and then goes off down any rabbit-holes that there present. Even these same-wavelength places have quite long fallow periods where there is nothing that captures my imagination - heck, that might be me in one of my downers. Then there will be a flurry of stuff that calls [yoo-hoo, you!] to be followed up.  If we still had children at foot, or I was a proper farmer, or I rejigged my course notes every year at The Institute, then I wouldn't have time for butterfly hops about other men's flowers.  Then again, I didn't start bloggin' myself until I was furiously busy at a new job and only a week ahead of my students.  I wouldn't say something like "If you want something done, ask a busy person to do it." that was Lucille Ball, I just lived it.  aNNyway, one of those jump-stations is Metafilter aka The Blue and the other day I saw a piece about role-filling in heterosexual relationships; that in turn was citing an original source. That source is interesting because it helps builds my knowledge of contemporary colloquial French because the author Emma is a thirty-something cartoonist who writes in French Faillait demander but gets her stuff translated into English You Should've asked when it goes viral. Her bailiwick is "Politique, trucs pour réfléchir et intermèdes ludiques"; which is whatever is floating her boat this week.

When I worked in the zoo in Rotterdam in the late 1970s, we all mucked [literally a lot of the time] in together but joked [*] that some of the daily tasks were vrouwenplicht - women's duty - while others were for The Men. As the latest addition to the team, I did all the [vrouwenplicht!] cleaning and polishing of the front panes of all the aquariums as soon as i started work and before Jan Publiek was allowed in to grub them up with their poky, pointy finger prints.
*you could make such jokes in those days without
fear of being called up by an Offense Tribunal.

Emma's position is that, although modern chaps fondly believe [ahhh bless, 'em] that they carry half the sky around the house -
  • they change diapers nowadays, 
  • can wash dishes or or at least load the dish-washer
  • can clean a toilet and mop the bathroom floor
  • cook up a storm for eight on the weekend - esp if barbecue involved
  • as well as the [bizarrely: who makes these decisions?] manly stuff
    • take out the trash
    • mow the lawn
    • wash the car
    • fix light-fittings
in fact all the mental heavy lifting is carried out by women.  The extensive commentary on Metafilter seems to agree.

We live in changing times! My father never changed a diaper in his life. I could and did; both in the 1970s with The Boy and in the 1990s with Dau.I and Dau.II. I could also sew on a button, turn up a trouser-cuff, cook, bake flapjacks, wash dishes and saucepans and clean a bath. But I remember, when Dau.I was about 8 weeks old, I was tasked to look after her for several hours while The Beloved went to a business meeting in town. At the end of the afternoon, the child was clean, fed and uninjured BUT diaper bin hadn't been emptied; there were dishes in the sink; the laundry was one wash behind schedule; the bed was unmade; and I had no idea whether there was sufficient tea, sugar or eggs in the house. I sent a You Should've asked link to the family and got two responses.
  • One from The Boy pointing out that the French do less housework than any other civilised country.  Skeptix alert: that is published in a British newspaper; an average of 16hrs/wk in France compared to 19hrs/wk in UK and you may be sure that stacks of ménages français do more [and less] than the UK average - the data distribution is going to be heavy on the variation and low of the average.
  • One from The Boy's partner: "SO not true in our house!"
That tells me that, in one family [so anecdote not data!], over three generations, The Man is stepping up to the plate and not just stepping up with a plate waiting for it to be filled.

Tuesday, 13 June 2017

Having it all

The intellect of man is forced to choose
Perfection of the life, or of the work,
And if it take the second must refuse
A heavenly mansion, raging in the dark.
When all that story’s finished, what’s the news?
In luck or out the toil has left its mark:
That old perplexity an empty purse,
Or the day’s vanity, the night’s remorse.
WB Yeats b 13 June 1865
As I am reminded by word-a-day today is the birthday of W.B.Yeats. As it happens, two years ago on his sesquicentenniel, I had a go at the dichotomy in the poet's life expressed by his poem The Choice quoted in full above.  A case could be made that Yeats was both pompous and self-regarding and his pursuit of Maude Gonne was annoying and her daughter goaty, but some of his poems sing in a way that they can be readily appreciated by children. Others are full of references which boiled up to the surface from the turmoil in his mind and finished up on the page.  That makes him a suitable subject for scholarly research and the bane of the lives of Irish students sitting Leaving Certificate English. That's what they do in the Arts Block - try to track down the references and sources of poets long dead.  That's why it's important to speak to creative people now before they schlep off to the heavenly mansion - saves time later when all you have is a bunch of letters and manuscripts.  You can check out the spoken word of , for example John Maynard Smith, at WebOfStories.  Then again, if you ask people - Harlan Ellison - Cédric Villani - where their ideas come from they'll probably have a madey-uppy story that is only partially true.

ANNyway, contra Yeats, I am sure you can live both a virtuous life and create a body of work that will amuse and edify after your death.  Not tooo virtuous, that would be boring but you should try to live the life you have rather than think too much about positioning yourself in posterity. It is most likely that you and everything you did/wrote will be entirely forgotten 50 years after you peg out . . . except by your grandchildren. As evdence I offer the difficulty I had trying to locate a single photograph of Jane Gibson.

This gives me an excuse to recommend Michael "Moneyball" Lewis's 2012 commencement address at Princeton.  It is a nice exercise in humility and hubris in recommending that we at least pretend to believe that nobody makes their own fortune. It's not really to do with naked ambition getting to the top by placing a boot in the faces of those under him on the ladder; we can all escape from where we started if we form an orderly queue.