Friday, 31 January 2020

Off label

This is the second year running that I've gotten to supervise students in our MSc in Pharmacy Regulatory Affairs [PharmRegs to most of those involved]. They are like any other group of students, some smart and engaged, some who need more support. The baseline that underlies their independent research projects is the licencing of drugs and devices by regulatory bodies like the FDA and EMA. These bodies prevent Pharma Companies (and anyone else) from selling drugs or devices unless they are a) safe enough b) actually work as described.
Q. How does the industry (producers, regulators and marketeers) make these crucial decisions?
A. By carrying out trials of animals and people and monitoring the effects of particular doses of drug.

One of those dose-levels is nul nix nada zero - these are ,placebo alert> the controls, lest the observed effects are due to the care and attention of the trial and its staff rather than to the drug itself. A good trial will try to measure all [or many] of the observable changes. It's not good enough to design a drug to control cardiac arrhythmia and only look at the traces from the EKG. Most drugs go in through the mouth and get to their destination by the circulatory system which will wash the stuff everywhere and have all sorts of effects. These are invisible if you don't look for them. In 2017, I wrote about how Viagra stiffened the sinews of a hypertension drug-trial that was about to be closed down for lack of significant  effects. That same essay addresses the re-purposing of Thalidomide as a singularly effect remedy for the symptoms of leprosy.

But here's  the prob. Once the drug-or-device is approved for sale, it is available for whatever purpose a rural GP [or indeed any doctor] sees fit. Take Olanzapine aka Zyprexa a rather effective anti-psychotic widely prescribed for schizophrenic voices and visions and bipolar disorder. But you don't have to look far to find "Not approved for dementia-related psychosis, because of increased risk of cardiovascular or infection-related mortality" - it tends to blow a gasket in the blood vessels of the elderly head to precipitate a stroke. So it's definitely not suitable for dealing with my elderly mother's Charles Bonnet visions. A few years ago one of my elderly relations went quietly and then more insistently off the rails. Everyone around could handle the increasingly complicated saga about Elizabeth Windsor, The Pope of Ratzinger, our own Michael D. Uachtaráin and the corgis in the Vatican cellars . . . so long as it stayed in the kitchen. But when the tale acquired legs and began to bother the local police-station, something had to be done. The local geriatric care centre brought the old chap in and prescribed . . . Olanzapine! Clearly this was one of their standard remedies because it worked: it dealt with those annoying psychoses - so distressing and awkward for the family and his carers. And the few cases where it all went horribly wrong didn't return to the geriatric suite but two floors up in the cardiovascular stroke unit.

I mentioned this to my roomie at The Institute who works the other half of her life as The Pharmacist in one of the town-centre chemists. She was not surprised but you could see she was annoyed at yet another example of hubris [overweening arrogance inviting disaster] from the medical profession. Some of them really are a law unto themselves, and they are not compelled to keep up with the medical literature to find evidence that what they think is correct is in fact dodgy if not outright incorrect. What really impressed me about my roomie's response was that she knew immediately the name and contra-indications of Olanzapine . . . and by extension any of the drugs in the British National Formulary.

Thursday, 30 January 2020

Doctor becomes Dave

Q. Hey, what do you call the chap [it's always a chap] who
graduates bottom of the class in Medical School?
A. Doctor.
In a way that's proper order: someone has to be last and at least that person completed the course, doing most of the assignments, attending many of the classes and presumably did well academically in school to scrabble the points to get into Med School in the first place.

Years ago a PhD fell into my lap [because I travelled to a different continent and worked really hard and learned  a lot]; in that case D is for Doctorate. But the only person who used that honorific was my mother when addressing envelopes (with stamps, remember them??):
Dr Robert T. Scientist PhD
she'd write. My son, the Doctor, indeed.

Well, as I wrote, my mother died recently and my siblings and I spent a weekend together in the parental home sorting papers - and other bits and pieces but mainly papers. Begob but there were a lot of them: mostly in cardboard grocery boxes where they formed archaeological layers. It's the kind of situation where a forensic scientist would be careful retain context. An undated letter near an envelope with a post-mark can be placed in historical context; Christmas and birthday cards tend to be in the same layer; an adjacent electricity bill can help predict which birthday was being celebrated; contrariwise a 90th bday card [must be 2010] can help date the adjacent concert programme.

Yes, yes, but none of us was treating it as a crime-scene, we just wanted to abstract family letters and photographs, and the most recent bills and bank-statements. The latter for probate to see how much tax we owed the state. My sister came across some correspondence from a ship's chandlery about 'preference shares' and 'dividends". The company name was familiar to us all because we'd each inherited 233 such preference shares from my father's Aunt Anna. Those shares were worth a nominal £1 each but were essentially valueless because when I tried to sell them through the company 30 years ago, they refused to entertain my request.

For probate-completeness, I was designated to contact the company to ascertain the value of my mother's shares. I got a surprisingly effusive response. The new Managing Director had acquired the Chandlery more than a decade ago and decided to clean up the company accounts by buying back all the preference shares. In 2011, he had squared away my mother [in 2008], and almost all the other holders-of equity; but there were still a few outstanding share-holders whom he'd been unable to track down. No, he had no recollection of a B. Scientist in the MIA list but he did have a D. Scientist and a vague suggestion that D could really be Dr. Scientist. That's me, I cried: Dr B.T. Scientist, PhD.  I even located the original share certificate from 1975.
 I now have Great Expectations of a few hundred pounds of 'found money'. It's really not so much the money as a useful exercise in consolidation and simplification of my financial affairs, so that my kids are not left with a huge heap of very miscellaneous papers and a mammoth headache.

Wednesday, 29 January 2020

Il Signore è il mio pastore

. . .  nulla mi mancherà etc.

Last Sunday I was tasked to read the 23rd Psalm; in a church; from a pulpit: so everyone could see me. As the Vicar said in his address later on in the service, Psalm 23 is very often read at funeral services because a) it mentions death b) it is hopeful about the future. In the Church of England it used to be that the King James Version [KJV] of 1611 was ubiquitously used. It was from close study of the KJV that I won the Junior Scripture Prize at the age of 11. But in any conventional setting, it is a good idea to shake things up a little to make folk sit up and pay attention rather than letting the words wash over them in a warm flood of unconsidered familiarity.

So my first thought was to read it in the John Wycliffe's first English translation which was published in 1384 more than 200 years earlier than the KJV and nearly 100 years before William Caxton brought printing to England. Wycliffe was a contemporary of Geoffrey "Canterbury Tales" Chaucer, and both are readable with a little effort because their Middle English is a longish way from wot we txt now.  I share Wycliffe's words with you here [his bible calls this the 22nd Psalm]:
  1. The Lord gouerneth me, and no thing schal faile to me
  2. in the place of pasture there he hath set me. He nurschide me on the watir of refreischyng;
  3. he conuertide my soule. He ledde me forth on the pathis of riytfulnesse; for his name.
  4. For whi thouy Y schal go in the myddis of schadewe of deeth; Y schal not drede yuels, for thou art with me. Thi yerde and thi staf; tho han coumfortid me.
  5. Thou hast maad redi a boord in my siyt; ayens hem that troblen me. Thou hast maad fat myn heed with oyle; and my cuppe, `fillinge greetli, is ful cleer.
  6. And thi merci schal sue me; in alle the daies of my lijf. And that Y dwelle in the hows of the Lord; in to the lengthe of daies.
Much as I was taken with being nourished on the Water of Refreshing, I found that the sense of "made fat my head with oil" has shifted so far in modern English as to be humorous rather than implying a blessing and benediction. So I scrubbed the idea of reading 14thC Middle English but still thought to ring some linguistic changes. In honour of the fact that my mother started to learn Italian in her 70s to get more out of her many cultural tours from Assisi to Zungri, I started my gig with
Il Signore è il mio pastore, nulla mi mancherà
The Lord is my shepherd, I shall not want.
On one level it's a bit pretentious gittery but then again it hints at the fact that my mother was quite comfortable talking with anyone: ratings and admirals; tanned and untanned; domestic or foreign.

Tuesday, 28 January 2020

Backup but Checkup

I was writing about the necessity / virtue of keeping copies of things in case one of them "makes like a wheel and rolls away".  This only becomes real when you are caught with your pants down and suffer a painful sting on the ass because you neglected this chore. Last week in class I was critiquing and correcting a Literature Review for one of my students. I am a strong advocate of using keyboard shortcuts in MS-Word: far quicker than piffling about with a mouse, let alone with a mousepad on a laptop. I was on the 3rd page when abruptly Word disappeared off the screen along with all my edits. Dang! But I'd only been at it about 10 minutes and could remember most of my suggested changes. Probably my fault: working on an unfamiliar keyboard I must have typed ctrl-S, ctrl+N or ctrl+Q. It took me 8 minutes to restore the status quo ante.

Back in the noughties, I was hired to work in one of the very first labs wholly funded by the new SFI - Science Foundation Ireland. Instead of piffling about with dribs and drabs of science funding the government decided to invest a Lot of money in cutting-edge scientific research. As a pilot study in how to spend the $pond$,, SFI solicited applications for five [5!] biotech research projects and five [5!] IT ditto. Ken Wolfe secured one of these prizes, was given some millions of €€€s and told he could hire the smartest people in the world who were happy to work in Ireland. Even with an unconstrained budget it was quite hard to get the money allocated in a way that would satisfy a government audit.
  • Personnel: The salaries were pitched very high, even for post-graduate students, but there was a limit to the number of seats that could be filled. Even a walking genius can't supervise 50 people working on 10 different sub-projects and there was a physical room with a finite number of electrical sockets. Those hired were indeed all super-smart but super-nice as well and it was a really productive fizzing place to be. I never figured out why I was hired but my imposter-syndrome died away as I started to get to grips with my tasks. Those who didn't die, did really well afterwards. And I think it's fair to claim that some amazing work was carried out.
  • Kit: everyone in the group was given a brand new high-end desktop dual-boot linux/windows PC . . . and a ditto laptop, so we could be productive on the bus. After 3 years we all got newer slimmer more gutsy laptops.
  • Expenses: one of the hires worked part-time as Office Manager and dealt with all the invoices, room bookings, petty cash and biros . . . as well as churning out a couple of papers a year with the boss.
  • Common core: part of the ancient Victorian office suite was partitioned off as a machine room, where a couple of the techy hires built the lab's own massive parallel server cluster out of Intel chip boxes [no I don't really know what that means, either]. There were layers of redundancy built into it so that, if one of the components failed, no data would be lost. 
  • Infrastructure: All these planet-sized brains, generating eye-wateringly large datasets, couldn't be expected to back up the day's work on a CD or USB key. No no, all the computers were backed up every Friday on a rotating set of DAT tapes and incrementally backed-up [all new changes that week] every night.
  • SYS$OP: one of the two techies, as well as churning out a couple of papers a year with the boss, was the designated Technical Manager fixing and advising on all the hardware issues and responsible for care maintenance and back-ups
Everything went along fine until two components failed in the server cluster and a chunk of data was lost. Not mine, praise De Lawd, but two of the post-grads lost weeks of data accumulation and analysis - >!poof!< gone without even a noticeable puff of smoke. But it's okay, said the Sys$op when he rocked up mid-morning [owls and larks were both tolerated], I'll restore everything from tape. But when he got there, the tape-cupboard was bare. All the tapes were there, but somehow an assumption had been made that they were all being written to each night. Indeed they had been  so written when the system was set up and checked but somewhere with the passage of time the current data hadn't been caught. I never wanted to find out the details of what went wrong, there were enough red faces without having to account to me. The corrupted cluster components were sent, at vast SFI expense, to a commercial data recovery services. But the discs were so badly corrupted that nobody wanted to trust the fragments of recovered code and those affected more or less started again from scratch. Quis custodiet ipsos custodes? - Who backs-up the back-ups?

Monday, 27 January 2020

Tweaking the microbiome

Only connect!

We could weather a lot of the crap that dumps on us through life if only we weren't already compromised in some quite distinct way. Being caught outside in a deluge is okay if you've packed an umbrella; you don't get Guillain-Barré syndrome unless you've been struck by Campylobacter or HPV vaccine AND you have a genetic pre-disposition. Did someone say vaccination? Seems that for some people, 'flu vaccine can trigger narcolepsy. I've had a lot to say about the microbes of our guts and how they affect our health and happiness. Why just the other day I reported that some people will gee up their immune system to an annoying intolerance of gluten IF their immune-system is programmed to react in that way to the natural (and almost always benign) zoo of bacteria in their guts. At the end of that essay, I suggested that it was diffcult to precisely promote the death of baceria known to be harmful, but that you might be able to preferentially feed 'good' bacteria.

Two days later, because the internet loves me very much, up popped a story about that very matter. It was doubly interesting ecaue I've got a final year project student who is looking at the genetic make-up of viruses which infect Listeria monocytogenes she is also looking at the mechanisms that Listeria uses to control the depredations of, and limit the damage caused by, these infectious particles.
A group of microbiomologists from San Diego [press release / exec summ] led by Lance Boling [L above] in the lab of Forest Rohwer [R above] have coursed over the literature to identify 100+ foods and food products that are claimed to be specific for affecting the microbial community in the gut. Among these foods are Stevia, a key ingredient in Gwyneth Paltrow's woo-wah fashion-accessory 'foods' or Goops as she prefers to market it. Other tested foods include citric acid, caffein, capsaicin, cabbage, cinnamon, clove - and that's just the Cs.
They have then tested these compounds to see
a) whether they killed such bacterial star players down there as Bacteroides thetaiotaomicron [prev] Enterococcus faecalis, Staphylococcus aureus and Pseudomonas aeruginosa.
b) whether the bacteria grew better "yumm: send more cottage cheese"
c) whether and how they affected the viruses that they deduced from sequence analysis infected the bacteria.

One of the key metrics used by Team San Diego  to count the cases of the change from lysogeny to the lytic phase of the viral life-cycle. Lysogeny is when the virus genetic material is physically incorporated into the bacterial genome where it lies dormant; getting replicated passively every time the bacterial host divides. This can go on forever . . . until something induces the virus to excise from genome, actively assemble dozens of whole viral particles and burst out of the bacterial host to infect dozens of other bacteria. That 'something' trigger might be a sense that the bacterial host is in trouble and like to die. The virus would be better off if it sent a great many descendants out to try their luck in the cruel world than passively wait for the end with and in the current home. This make copies and scatter is called the lytic phase, because it involves the lysis of the bacteria.

The original paper, replete with data and informative graphs is freely available, so you may go and mine the horse's mouth for things that you may like to include in your new rich and varied and pre-biotic diet. You may bet that there will be some problems with replication - another strain of Bacteroides thetaiotaomicron might have a subtly different genetic make-up but this is grist to my mill of reflection on the relationship among diet, microbiome and health. It's in the detail: Arctostaphylos uva-ursi [bear-berry] will cause massive virus induction in Bacteroides thetaiotaomicron but tends to prevent this bacteriocidal phenomenon in Enterococcus faecalis and Staphylococcus aureus. If one food product doesn't do much then there is always the possibility of synergy on the plate: a salad of chicory, clove and cashew may turn out to be just the thing for duffing up Clostridium difficile.

Sunday, 26 January 2020

Tea-time of the soul

A few things to clear the head

Saturday, 25 January 2020

trees make books

Margaret Atwood [L] gives a Masterclass. You become a writer by writing, there is no other way! She talks (graciously) to a couple of young wans.
Tip number 1: get a notebook.
How To on BigThink
Tip number 1: get a notebook.
I wish she would talk to our students! When I am sharing my insights about human physiology or water chemistry in front of a succession of powerpoint slides only a tiny fraction of the students in the room write anything down. They are confident that they will remember everything in May for the exams - but they are wrong. They will have forgotten 90% of what I've said by the next weekend. Even in one-to-one meetings [without powerpoint and considerably more rambling], students rarely have a note-book open and, even if they do, rarely write down what I tell them.

I'm writing about Atwood because of a neat story sent to me before Christmas by my pal Dec. Framstidsbiblioteket is a project dreamed up by Katie Paterson a concept artist from Scotland and she has recruited Margaret Atwood to write a book that neither of them will ever see in print. Paterson has mobilised a team to create a Norwegian Wood [not Beatles] that will grow for 100 years, then be felled, logged, pulped and used to print limited editions of 100 previously unpublished works. That's pretty aspirational: there are A Lot of ducks to put in a row: foresters, conservationists, regulators, legislators and curators; let alone authors, editors and curators. Preserving something for a long time is full of uncertainty. It is not true that Walt Disney's brain is sitting in a cryopreservation tank until a cure is discovered. Only a tiny fragment [7/123] of the works of Sophocles have come down to us in the 21stC. And no pressure on Atwood to devise a work that will have anything to say to the people of Dublin as a commute about the city in dinghies.

Friday, 24 January 2020

B is for Archivist

Like I said, my mother died earlier in the month; in England so the whole process of wrapping up has been a long drawn out affair. I don't think that the process of dying takes longer in Ireland or England: that depends far more on the consultant in charge of the hospital bed and how willing s/he is to accept that This One is not going to make it. An almost retired pal of mine who works as a GP in the country shared a reflection from a previous even older incumbent of that GP practice. Towards the end of his 60 years of caring for his neighbours he became increasingly reluctant to send any of his patients to a nursing home, let alone hospital. "I've seen too many farms eaten to nothing to pay for medical expenses for someone who will never get better." The family cannot easily articulate such a thought because they care, but also because [some of them] need to be seen to care. It is often the son, daughter, niece who has been living and working furthest away who is most insistent that Mam gets Everthing the tax-payer, through the care-team, can thrown at her.  It's so easy to be demanding when you don't have to change the fouled sheets yourself

My mother tried it both ways:
Accepting in September a non-surgical intervention that would deal with the immediate, distressing and dull-aching symptoms.
Refusing further treatment when those symptoms returned four months later with a great deal of mess and pain.
Four months is a long enough time to reflect on your own mortality if you allow your intellectual mind to process the data and damp down the emotional turmoil of having to confront oblivion.

My brother and sister and I had agreed to spend a weekend together in the old house a) to please our mother with the idea that we could act like a family b) to process some of the accumulated gubbins that our parents had accumulated since they were born in 1917 and 1920. Cunning plan a) only happened if you believe in an afterlife but we definitely put in two days going through boxes and suitcases of Stuff . . . together. Well, formally and pedantically, we were mostly working in separate rooms to get space to create different stacks: discard - discard confidentially - for him - for her - for me - for more distant rellies - for outside bodies.
One of my coups was to unearth a letter sent by my father on 9th April 1957 to 106 Barrie Street, Kingston, Ontario. That's where we actually lived when my father was stationed for year in Canada to represent the UK Navy in a long-running NATO think-tank and planning exercise. #106 has been demolished and replaced by the the grey 4-storey apartment complex visible behind the photograph of #98 and #100 [above]. A few years ago, I was expected to report every address I'd lived at since I was born to prove that I wasn't going to abuse any young people I had to work with. I phoned my mother to ask where we had lived in Kingston, ON about 65 years ago. She said it was opposite a park in the oldest part of the city. I went on Google maps and reported #7 Rideau Street as the place where I first ate [part of] the contents of a sandpit. I was only 800m off target in a NE direction! That would have been a mighty score for Geoguessr. I shall write to the Gardai immediately, confessing my error, asking for the record to be amended and hope that the paedopolice don't come and take me away.

I have brought away a short stack of 5 decades worthy of my own dutiful letters to the honoured parents. The pathetic illiterate scrawls of 10 y.o me eventually started to fill out with biographical data when I took myself in hand at the age of 15 and developed a script that was fast, neat and legible. I am under no illusions that anyone is going to want to research or write my biography but I am now trying to add dates and places to the letters, so at least they will be in chronological order. The family policy quickly agreed that letters and cards to the parents from people we'd never heard of could be dumped. Photographs, especially if pre-WWII were given a stay of execution in case anyone from the wider family might recognise their own parents. But really, a picture of a Victorian gent leaning against the edge of a portico with no attribution on the back, what use is that?
Note to archivists: date, name, place on the back of all photos. 
Too many photos for this to be feasible? 

Thursday, 23 January 2020

Uncle Bob advises

A couple of weeks ago, my HoD sent out a call for volunteers to serve the Science desk at the evening Open Day. My reaction was meh! I gave already. Then on Tuesday, the call was repeated with "Refreshments served in the annex from 4.15-5.15pm" to which I replied (ASAP lest my response be lost in the stampede from the voluntariat):"Jakers, why didn't you mention the refreshments first time round?" Which committed me to start grazing at 1700hrs on goujons, spring rolls and doubtful sandwiches filled with mayo-and-meat. Not really a balanced meal but I was a graduate student once and find it hard to refuse free chop.

The evening Open Day is a different, more focused affair than the big daytime events when coach-loads of uniformed teenagers are disgorged at regular intervals through the morning. Most of them just relish the chance of a day off lessons to roam around the concourse in packs. Last night was much quieter and the punters had a much clearer idea of what they wanted to do. Far too many parents, though, most of them Mammies speaking for their teens. The Institute offers one Aggie course, at our satellite Campus down on the coast, called Sustainable Farm Management. It's run by a couple of my pals who, as well as the day job, are real farmers in the next county. I am happy to recommend it for people who don't want to go to college in the city.

I got one enquiry about the SustFarm course, from a young woman [and her Mammy] from a dairy farm in Westmeath. I asked how many acres they had, which elicited a prim "I'm not at liberty to say" in case I was going to grass the family up to the Revenue Commissioners. We chatted on about the course and then I had a brainwave:
Why do you want to do farming at college? You've spent your whole childhood in the milking parlour, there's not much you don't know about the business; would you not think of doing something different. Bring something back to the table after your four years out in the wild?

I tried to think of something completely different . . . humanities . . . French . . . Tourism!  Lookit, I said, you need to diversify; all my farming neighbours are diversifying because it's impossible to balance the books with sheep and subsidy or milk and subsidy. You could come back and set up a corner of the farm-yard as a petting zoo or make artisan jam. And remember Paddy and Joyce O’Keeffe from Clogheen, Co Tipperary. They were fed up getting up at 4 am seven days a week to milk the cows to sell it to the creamery at 12c/lt. They decided instead to add value  at home and sell ice-cream at the farm gate. Within a few years they were buying milk from other diary farmers in South Tipp and retired on their money in 2008. Ice cream is a bit yesterday but what about organic yoghurt or . . . koumiss! Three years ago, at another Open Day, I tried bullying a young woman into making soy sauce for Ireland.

Wednesday, 22 January 2020

Cut your cloth

The Institute offers a number of post-graduate courses, mostly through our Night School. If I leave work at 17:00 the concourse is eerily empty; except that the cleaners are doing the floor and emptying the bins. There is little appetite for working a minute over 9-5 M-F, so there can be a bit of a log jam getting through the door to the car park at 17:02. But if I am unavoidably delayed at my desk and leave after 6PM then the place is starting to hum again. Evening classes start at 7PM and it looks like people go straight from work to college to meet their pals and have a coffee before class.

Christmas 2019, I was asked if I was interested in supervising a student [or two] in one of the bioscience/business taught MSc courses. For the MSc, they have lectures every Tue and Thu evening for 2-3 hours but they are also requested and required to carry out an independent research project. This 'thesis' is cut to the aptitude, ability and spare-capacity at work of each student. A mentoring gig pays me for 12 hours of contact time to help extract a chunk of original research from each mentee . . . and correct the structure, intelligibility and apostrophes of the finished product.

I want all my students to do the best they can and a little bit more. The poor lonely, cold, young chaps from Southern India who first spoke English as a teenager in High School won't have as much to say as a middle aged Irish line-manager with 20 years experience in the industry. But both those exemplars will rise to the challenge and turn in something at the end of this Summer. This year one of my mentees is biddable, polite "Don't call me, Sir!" and a bit lost. His research proposal is a bit of a boiler-plate Compare the Regulatory Protocols for [insert drug-or-device here] in the EU vs USA. I dragged him off to the library to look at a previous thesis doing a FDA vs EMA comparison. Then I told him he couldn't cover every drug in all its Regulatory aspects if he was going to do, say, 10 hours research and writing every week for the next 26 weeks. He'd have to focus on a chunk of that Universe and diligently try to abstract the data, analyse it in some way, and write up a coherent and interesting report. Jaysus, it has to be interesting - to student and reader - with the whole universe of Pharmacy regulation to choose from, you have no excuse to be bored and boring.

What is a MSc-worthy chunk, Sir? his eyes pleaded. I grabbed his note book [at least he was taking notes, which is not always the case in these interviews] and sketched a diagram [like above R] to indicate three possible solutions to his dilemma.

  1. Scatter-gun [open squares]: these 8 student-hour blocks represent a full quota of 260 stud/hr work. That's a lot of work, yes, but between them they do not answer any question or aspect fully or comprehensively
  2. Take a slice [hatched column]: start off with a really narrow sample from the drug  universe and cover oneclass of drugs for one aspect of regulatory detail. If that takes a week, then expand the number of drugs OR the regs so you finish up with either a solid vertical or solid horizontal bar of research.
    • It's up to the student to gather the data, marshall the evidence [I've not had 100 hours of lectures on Pharm Regs, so haven't a clue where to start]. I can help with forming the hypothesis and the statistical analysis - that's generic. 
  3. Worse case [splat]: make no attempt as comprehensiveness; pick a bit of this and a bit of that; lash it down on paper any which way; do no statistics.
I did have one good idea about data access. If it turns out that data is more easily obtainable from the FDA than EMA it would be prefectly legit to do "Comparing the time taken for regulatory approval by the EMA for antibiotics against Gram+ve vs Gram-ve bacteria". That's a slice that ignores [the boring predictable] EMA vs FDA transAtlantic comparison but nevertheless delivers some data to which a t-test or a ChiSq may be applied.

Tuesday, 21 January 2020

Jaysus, give up the ould statins

At work in The Institute I'm perhaps too willing to help out. Then again, with an empty nest at home, I have a bit of spare capacity and why wouldn't I volunteer for a recruitment drive or a student experiment or the annual science fair? Last year, I undertook to thesis-mentor three (3!) MSc students on the Pharmacy Regulations course. One deferred graduation because he was super-busy at work In MegaPharma Inc. shuttling between Carlow and King of Prussia, Pennsylvania so I am only now reading his (deferred submission) thesis. I told myself never again, but I was asked nicely by Life Long Learning to help out and have acquired two more PharmReg MSc students. Dang! Far too many of these theses are "Comparing the regulatory systems for [insert topic] in the USA [FDA] vs EU [EMA]" . . .yawwwwwn. But the bottom line is interesting:
For any drug or device, the EMA almost always takes longer than the FDA to process the licencing application [fact] . . . because the Feds care less about the risks [supposition]. Licensing requires success on two complementary fronts
a) Efficacy the drug must cure or increase QALY for some people some of the time
b) Risk do not kill, disable or make miserable too many people from the side-effects. The FDA will give MegaPharm a pass on Risk: the EMA is more primly risk-averse, so takes more time.

Why side-effects? Because oral meds are a really blunt instrument. Biomedical research has the most superficial understanding of what goes on inside. We only have 23,000 protein-coding genes to make the enzymes and receptors which control all the peculiar and particular metabolic processes essential for life as we know it, in trillions of subtly different cells. Some of these molecular entities must be double-jobbing. And they are:
Is it any wonder therefore that when you pop a massive dose of a bio-active chemical [it has to be massive to pass through the stomach, get absorbed by the gut, avoid being de-toxified in the liver, be diluted in the blood-stream to encounter a set of receptors in a few cells of one organ of the body] it has effects elsewhere than the intended target?

All this back-story came crashing towards me as I read a long form BBC essay The medications that change who we are on unwanted side-effects.  Frightening stats in there: US consumes 50,000 tonnes [= 50 bn grams] of paracetamol each year enough for 300 pills/yr for every man-woman-and-child.
Statins, the cholesterol-lowering drugs are very widely prescribed by Irish doctors, [press release NUIG with BMJ link] indeed they are lashed out in handfuls across the First World for anyone whose cholesterol is above some arbitrary threshold. I was given the option when my last MOT showed my cholesterol was high; I said I'd keep the money and eat less bacon [I lied about the bacon]. Statins are cheap as chips [because the market is now so huge], especially if the government is paying [50% of Irish adults are on a medical card]. So there is a tendency to think that, even if the positive benefit is marginal at least they do no harm. Similar faulty reasoning about antibiotics saw them over prescribed for 50 years so we now have an anti-biotic resistance crisis with MRSA and CRE. For any medication it is handy to do a back-of-envelope number needed to treat NNT calculation. How many people have to take the drug for 1 person to be saved. I've done these for Ringer's /saline drips and prostate interventions.

Mais revenons à nos statins: It seems that for some people, statins can have frightening psycho-active side-effects: road-rage, domestic assault and suicide. Whaaaa!? But if you think a bit, it has the ring of truth. Statins lower cholesterol <butter!>. What is cholesterol <butter!>?
  • To a hammer doctor everything looks like a nail druggable target. Cholesterol is a small molecule that we are consuming <butter!> far too much, the body plasters the excess on the inside of blood-vessels because the enzymatic cholesterol turn-over mechanism is overwhelmed. Eventually, in some people, the cholesterol totally occludes the coronary artery, <infarction!>, the heart is starved or oxygen and glucose and the patient dies. 
  • To a human physiologist [that would be me, I've been teaching it for seven years now and I have a body] cholesterol looks like a small molecule with a strong structural similarity to aldosterone, cortisol, estrogen and testosterone. Why wouldn't cholesterol act as a hormone? Why couldn't tricking about with its concentration by statins have physiological and psychological effects?
If you think like the FDA you ask what differ? let's think on all those people who didn't have a heart attack. The risk-aware EMA  might be totting up all those weird rarely reported cases of road-rage and putting them in the balance. "rarely reported" because a) they are rare b) a lot of people just suck it up on the adverse side-effects especially if embarrassing - who wants to share their suicidal ideation; their feelings of fury towards their wife; their flatulence and diarrhoea ?? And it's not just statins: paracetamol, antihistamines, asthma medications and antidepressants have all been flagged for bizarre psycho-side-effects.

Does this make you think about Gardasil and HPV? After risk-assessment, I'm still on the side of mass vaccination of girls [and boys] before they start sharing bodily fluids but we really can't sweep those who have adverse effects under the denial carpet.

Monday, 20 January 2020

Trigger warning Pseudomonas

I eat a lot of bread. I eat more or less every crumb of sourdough that I bake: possibly because it is so tart nobody else will. I do a line in chapattis as well; using 85% wheatmeal flour, known on the subcontinent as Atta. The latter is ridiculously quick and simple; while the sourdough is hard work involving kneading, proving, knocking back, sticky fingers and an over-night of elapsed time. If I couldn't eat bread [and flapjacks, cookies, stollen, cake, shortbread] my quality of life QALY would plummet: rice isn't the same thing at all at all. There is a lot of wheat intolerance out there, even when you discount the neurotic foodies who think that spelt has no gliadin. It has! and here is the sequence of one such protein:
>A0A1P8DTE7_9POAL Alpha-gliadin OS=Triticum spelta 
For spelt Triticum spelta and reg'lar wheat Triticum aestivum, gliadin is a storage protein, quite insoluble, ready for emergencies when it can get broken down and recycled. For me and other bakers gliadin is an elastic stringy kind of substance which contributes to my sticky fingers but also forms sheets in the dough that hold the bubbles of carbon-dioxide to make the bread rise. People who are intolerant of wheat are reacting [symptom list do NOT read if hypochondriac] to the presence of gliadin with an inflammatory response: flooding the gut with water [bloating] and diarrhoea] to flush out a foreign substance. It's called c[o]eliac disease, or celiac sprue, or just CeD. You are very unlikely to get CeD, unless you have a genetic predisposition. HLA-DQ2.5+ and/or HLA-DQ8+ are the genetic variants to avoid if you're going all GATTACA on your next GM child. HLA is a determinant of the Major HistoCompatibility (MHC) genes: a super-variable component of the immune system which has evolved to give us an appropriate response to co-evolving pathogens.  Sometimes the immune system can get over-feisty and cause damage rather than clean up the bad guys. We looked at Campylobacter jejuni and how it sometimes triggers the development of Guillain–Barré syndrome afterwards. To some folks' immune system, something on the outside of Campylobacter jejuni looks remarkably similar to their own myelin sheath and having done for all the bacteria, the immune cells start to attack the periferal nerves.

You are almost certainly different wrt your HLA variants from the bloke sitting next to you on the bus. Buuuut, there is s good chance that your HLAs will match your baby sister's; which will be handy if she ever needs one of your kidneys. Variation in HLA is a major cause of transplant rejection. The peculiar thing is that some /many people who are HLA-DQ8+never go on to develop CeD and continue to scarf down toast every morning for breakfast with not a bother on them. It has long been suspected that there is an environmental trigger which kicks off the symptoms of celiac. But it is only now that we have a plausible microbiological culprit. A group of immunologists centred on Monash U. in Australia have published  a paper "T cell receptor cross-reactivity between gliadin and bacterial peptides in celiac disease" in one of the Nature journals. It's paywalled up the wazoo but they have carefully shown that numerous normal inhabitants of the human gut have proteins which are similar to human gliadin. The enzyme succinylglutamate desuccinylase (PFSGDS) from Pseudomonas fluorescens for starters. But other candidate triggers were revealed in Enterobacter cloacae and Acinetobacter baumanii. The Monash team have done a lot of work to show that the antigens on these normal members of the gut microflora are indeed recognised by T-cell receptors sensitised to gliadin. It's neat because it holds the beginning of a whisper of a clue towards a cure for sprue. Until we're really designing babies you cannot do much about your HLA status - except shake your fist at your cold dead ancestors. And with the crisis of antibiotic resistance you're unlikely to be able to selectively kill all the potential microbial triggers you have in your gut. But you can imagine that a peculiar diet might tilt the balance among your microbial flora so that the trigger-bugs are overwhelmed or driven into hiding

Sunday, 19 January 2020

Sunday 190120

I've done a runner to England. I'll leave some food for thought:

Saturday, 18 January 2020

Lord of all I survey

I came home one night in the New Year to find a fat envelope and a post-card stuffed behind a pot-plant on the windowsill. Not the postman - he knows better; but from Ipsos/MRBI the polling company, on behalf of the Department of Health. The DoH, in their Healthy Ireland initiative, had contracted Ipsos to carry out the National Household Study; a survey of a randomly selected 13,720 homes across the country to answer questions about
  • General Health
  • Smoking and quitting
  • The booze
  • Mental health and well-being
  • Social connexions
  • Health comms
  • Homecare services
What's not to like about participating? I live so rural (300m up a rough track and 500m from the nearest inhabited house), that it's nice to have someone visit. When I retire, I'll be sending myself letters and then pulling on the poor postman's lapel like crusty ancient mariner. Accordingly, I sent a txt to the number on the post card and said I'd be free for grilling on Thursday evening. Thursday came round followed by a vaguely familiar woman VFW knocking on the door with some ID and a tablet ready to survey me. VFW admitted that she'd been in our place four years earlier when she'd called as a Census enumerator.

She was a couple of years older than me, retired from the CSO and censusing, but doing similar work for a commercial company . . . for good money because Ipsos/MRBI's accountants wrote off almost all her tax against mileage and other expenses. I thought for half a tick that it might be the sort of thing that I could do for pin money in a year's time. Then again, I couldn't. It takes a certain type of person who is happy to knock on doors in the dark and ask people personal questions. Later on, when we came to questions about mental health and social exclusion I mentioned the fact that one of my neighbours had pitched himself into the river and drowned at the end of last year. "Oh you mean Paddy?". Whoa, forget about GDPR, it is not right to have people enumerating, questionnairing and censusing in their own community. It's just not anonymous any more, it has been filed in a mental rolladex of possible gossible. You see, she remembered from census times that I worked in The Institute and knew more than I did about an uncomfortable number of my colleagues.

Friday, 17 January 2020

Metropolitan Meelin

I'm reading the spooky fascinating and profusely illustrated Deserted Schoolhouses of Ireland by archaeologist Enda O'Flaherty. He has a website that will give you enough of the detail if you're too mean to buy a copy of his book. Not all the schools on his website are abandonned:
Affane/Sluggara school [1914] in County Waterford still has a roof and is being used as the village hall. In our neighbourhood, Rathanna National School has become the community hall serving funeral teas, amateur dramatics, subtitled films and Buddhist meditation to different section of the local population. Funerals bump meditators and cineastas off the schedule. 10km away, there is an active painting group in Killoughternane school which also serves as the jump off to regular pilgrimages to St Fortchern’s Holy Well down the road. All of these schools served the community which was within walking distance back in the day when there were a lot of homes in remote rural Ireland each housing a lot of children preparing for confirmation and emigration. Family sizes got smaller as people ignored the Pope's views on contraception. Small farms daughtered out and got consolidated into larger holdings. The old farmsteads fell to ruin after transitory use as byres or were bought by city-folk as a weekend bolt-hole. And over the decades since WWII, the school catchments have been consolidated also: one central school for an area previously serviced by several. School buses negotiating narrow winding lanes consequently make my morning commute hazardous.

One of O'Flaherty's dead-schools is Milleen NS in Co Cork. As an aside to his essay on the school building (also 1914), he shares the local claim ‘Welcome to Meelin – Ireland’s Highest Village’. Insofar as I think about that sort of thing, I had always accepted that Roundwood, Co Wicklow held that honour. Roundwood's population of 950 makes it a biggish village and its height is reported as 238m. Glencullen, Co Dublin is much smaller [N = 200 people] but a little higher at 251m and has one of Ireland's most famous pubs Johnnie Fox's. Meelin is 250m above sea-level. Meelin / Milleen / An Mhaoilinn, apart from being confused as to spelinge, claims to be 250m up; population here is ~600. The Irish do love their tea but this controversy about who has the highest village feels like a storm-in-a-tea-cup. How do they decide where the datum is? The post-office? The village pump? The church? The steeple? The average height of the townland?

Another reflection is how piffling these record heights are. Our front gate is 230m above sea-level and I don't think that any of us get altitude sickness. So many of our major conurbations are at sea-level: Arklow Belfast Cork Dublin Ennis Foynes Galway . . . are all tidal . . . all in the front line for climate change.

Thursday, 16 January 2020


Time was that The Blob was constructed in real time. I'd get up early, as I do, write my piece, post it on Blogspot and leave for work. Consuming a quart of tea and two slices of toast along the way. I'd often check the Wikipedia Main Page to see if something sciencey had happened overnight or if it was a significant anniversary - Joseph Hooker's birthday, that sort of thing. Then I discovered 'scheduling' which allowed me to clock up some time-insensitive copy on the weekends or the previous evening and set it/them to launch between 7am and 8am on a future morning. Old habits die hard, and I was scanning The Wik and it flagged the 1937 20thC Fox Fire when almost the entire archive of early Fox films went up in a mighty carbon footprint. It was probably a case of spontaneous combustion because early motion picture film stock was made of nitrocellulose.

The N in Nitrocellulose [R above] is the same as the N in TNT [R below] which I've written about before. Nitrocellulose is also known as gun-cotton and it's made by soaking cotton fibres (cellulose) in nitric acid. Gun-cotton is dangerously unstable: all those oxygen atoms are ready to combine with the proximate carbons to produce carbon dioxide in a violent exothermic reaction. This was discovered in about 1846 by Christian Friedrich Schönbein, who was chemisting at home (as you did back then), spilled some nitric acid on the kitchen table and used an apron to mop up the mess. He set it to dry by the stove, where upon it vaporised with a whoomph. His wife was delighted when she came home! TNT is a bit more stable, not least because the ratio of oxygen and carbon means that external oxygen and more heat is needed to get it going. Nitrocellulose will normally deflagrate like Frau Schönbein's apron. But if confined can be persuaded to detonate - shock wave travels faster than sound so !Krak!

Mais revenons nous a nos Fox Film debacle. Fox had contracted to have built an archive at Little Ferry New Jersey. Mindful of the unique resources to be stored the building was built to be fire-proof; and it was so long as the threat was external. Insufficient attention was paid to the flammability of the material to be stored:no sprinkler system, no watchmen, no ventilation. During a July 1937 heatwave, the nitrate film spontaneously ignited and blazed through the whole facility - and indeed out of the building too with flames vomiting out of all its orifices in 100 ft sheets. Nothing of historical or cultural value survived. 40,000 reels of mostly silent film had gone up with a whooomph! The only salvage was about $2,000 worth of silver from the AgNo3 which was the light sensitive compound on that old black & white film. You have to wonder why the company chose to store but one copy of the material. They must have believed the architect and the contractor when the said Fire Proof in a loud voice. Let that be a lesson to you in your escapades on your computer -
back up early and backup often!

Wednesday, 15 January 2020

Breath becomes air

My folks were married in August 1950 after a bit of a whirlwind courtship having met in Dover in March. In May, at Lyme Regis on the Dorset coast, he went down on one knee to propose and she accepted. The picture [R]was taken about that time: probably in the cold [note gloves: d'ye think they might have been holding hands moments before being surprised by the photographer?]; and possibly on the Front at Weymouth where they had their first home. Before three children came along to cramp their style, most weekends they pootled about the rolling hills and hidden valleys of Dorset in a little Austin A40 through Ryme Intrinseca, Shitterton, Bere Regis, Lytchett Matravers. Always together, sometimes in company of rivals on treasure hunts picking up clues from weather-vanes and pub-signs. They were good at puzzling things out because they were curious and read a lot and had travelled abroad during WWII and afterwards. I'd willingly recruit either of them for my pub-quiz team. Well I can't have that now because my father died on this day in 2001 and my mother died 19 years later just a week ago: 80 days shy of her 100th bday. Since being widowed, she had been living at home looking after herself: latterly subsisting on a diet of Port Salut, spinach and trout, with posset to follow. At the end of August last year she had a medical crisis, was hospitalised, patched up and discharged to a care home down the road in the next village.

To be frank, the Old Vic could be a bit scatty about delivering the meds and adhering strictly to special diets but you couldn't fault them on the caring. The staff had time for a chat. The Polish chef was always distributing slices of cake and petit fours, often personally; he too had time to chat. For  the first few weeks, my Mother was having a great time. The stress of shopping for trout and spinach when she was too blind to read the sell-by dates; and cooking the stuff without missing the saucepan when pouring sunflower oil; and washing dishes and finding a cleanish plate . . . all this fell away in the Old Vic. The food was hot, tasty and varied, someone else washed the dishes . . . and the en suite; and helped keep her clean and presentable. But after a short time eating in the communal dining hall ceased to be fun - "everyone else is deaf or demented, or both, so it's hard to hold a conversation". After one particularly unfortunate placement opposite a demented old lady with a hacking cough - "it was like trying to picnic in a hail-storm" - Mum elected to take her meals in her room. By late November she was reflecting that the four walls of her bed-sitting room were all the view she was ever likely to see. It wasn't strictly true: the room had french-windows giving onto a covered veranda with a rose-garden and a duck-pond beyond; and between a couple of tall trees the start of a rolling farm-stead with occasional cows.

A couple of days into the New Year, her symptoms returned in dramatic and painful fashion. She refused further interventions, especially going to the hospital which had killed her husband and settled in to await the end. It took a week to come and was not without struggle, confusion and turmoil, but with her much loved and total caring daughter at her bedside " . . . peacefully breathed her last at 0337 today; it was very quiet and simple. Outside there was a wild, warm wind in the trees so we opened the French window and let her fly free over the hills of Dorset which she loved".

I liked that touch very much, not least because it's not very British; although opening the window to let the soul out is traditional across Scandinavia  and rural Ireland (at least). I mentioned this to a friend who has strong connexions with the Connemara gaeltacht and she shared a story of her older brother holding vigil with an old neighbour's family as she measured out her last hours. The breathing stopped; one of the sons discretely opened the window-sash and everybody set to with a decade of the rosary . . . only to realise that their [g]mother had joined in. It was Winter, it was cold, the window was discretely closed again.

I could not forebear to add  "Nevertheless, I will share a nice story that was going the rounds when I started working in St Vincent's Hospital in 2001. In 1990, Ireland did surprisingly well in Italia 90, that year's World Cup soccer tournament. An elderly lady was occupying a hospital bed for her last journey surrounded by her anxious family. As the time for a crucial Ireland match approached, she told her sons and daughters to go off and watch the match in the common room "sure don't be worrying about me". After the game, her rellies trooped back somewhat sheepishly having had their priorities exposed. 
"How did we do?" murmured the old lady 
"We won on penalties" they chorused 
"I'm feeling much better, so; is there a cup of tea to be had?" The restorative power of tea (and soccer) worked its magic, she was soon discharged and lived on for several more years."

Tuesday, 14 January 2020

Dick the Engineer

Hey boys, you don't have to buy into The Patriarchy
As I start into my last year in the full time work-force, it is natural to reflect on what it all means: work, life, balance, the Universe and Everything. For the last seven years and seven days I've been toiling away at The Institute, a third level college in the Irish midlands. I think it's fair to say that standards and outcomes have slumped since I've been working there. There most indictable manifestation of this is having students fail some modules of their final exams in May and so boot their chances of securing an Honours degree; even if they pass the resit exams in August. It is indictable, and the teaching faculty and administration must accept some responsibility, because it is quite predictable who will fail those exams because there are students who are serial failers. But we've got them over the line with extra tutorials (and lowering standards?) and back-stop assessments again and again.

I have been careful to designate these chaps failers rather than failures, because I'm sure that they will have happy and fulfilling lives in fields and enterprises where their exam anxiety, dyslexia and poverty won't be a handicap. Look at Richard Branson or Orlando Bloom: the poster-boys for feckless, dyslexic, school drop-outs who eventually done good. The Institute has a vested financial interest in keeping bums on seats paying fees for the full four years; but we're not serving the un-bookish kids well or even fairly. They'll earn a lot more as a plumber than as a lecturer and they may as well start earning and learning their trade at 19 as at 23. One of the problems is that youngsters spend so much time in school and then in college where the most obvious and apparent adult role model is someone who did well in school . . . and became a teacher.

Two enterprising teenagers Cormac Harris and Alan O’Sullivan [R with excellent teeth], of Coláiste Choilm, Cork have just won the big prize at the BT Young Scientist and Technology Exhibition 2020 with “A statistical investigation into the prevalence of gender stereotyping in 5-7 year olds and the development of an initiative to combat gender bias”.  The everywhere retweeted soundbyte is that, when asked to draw an engineer, 96% of boys drew a bloke, but that only 50% of girls drew a female engineer. [BTYSTE - Silicon Rep - Indo]. “We saw that more girls were choosing subjects like Art and Home Ec, and boys were choosing STEM subjects like Physics or Construction and DCG,said Cormac. “So we were wondering where did this divide come from? So we decided that the best way to find out was to go right back to the beginning, to senior infants and first class and to carry out some tests to see what their views on gender stereotyping are,” added Alan.

The point was made that at the moment we're beating on girls to be more STEMy as if a) it was their fault b) they'll be happier getting the rewards of technological education. We could rather encourage chaps to cook and code and care which are, or have been traditionally, female roles. They might be happier there. As kids we rarely know how to become our true selves but it's almost certainly not what our parents and teachers hope and expect us to be.

Monday, 13 January 2020


"WooooooHarrr, one week down for the last term in my last year at The Institute. It's also just a tad over seven [7!] years since I started there facing an absurd wall of teaching requirements: . . . . density, Excel, fluoride, genes, homeostasis, iodine, jokes, kidneys, lithium, median, normality, osmosis, probability, quality-control . . . I have a really good HoD, who deserves all the support she can get, so I try not to get all prima donna about the timetable. The year is a game of two terms but  some courses are taught only before or after Christmas. The first week my sole Monday class was Remedial Math / Computing at 4pm! That's a lot of diesel (90 minutes, 80km roundtrip) for an hour's work but I figured that I could / should devote the rest of the day to marking lab-copies, prepping classes and thinking up easy exam questions.

I did make one request, though, which was to consolidate my two Research Methods ResMet1 classes into a single back-to-back 2 hour block. The Gaffer could accede to that request, but only by scheduling the class 1300-1500 on Friday. She also mentioned that would have the effect of bracing up another Friday afternoon class for that group which was scheduled for 1500 = 3pm. I knew what she meant because the working week is effectively being reduced from M-F 9-5 to a 4½ day week. Several of my students in the 4-5 classes seek my appro to leave the room at 16:45 "to catch their bus home". That's fine with me of course, if the kids don't want to be there, then compelling them isn't going to achieve the dreaded LOs - Learning Outcomes.

I told my Friday arvo ResMet1 students about how 2 hours back-to-back [with a ten minute tea & pee break] was better for everyone than two unattached hours on different days - the activation energy is less for the second hour because we're all in the zone. Because I R old and clearly a silverback from the last century, it is not completely out-of-cliché for me to have a little dig at The Youth of Today. With my tendency towards over-sharing full disclosure, I also told them that our Friday class was designed to encourage attendance for their subsequent class. "Not no more", they replied, "the lecturer has shifted that class to Wednesday". Well really! That lecturer is a particular vital and engaging chap but still very young in my eyes, and seemingly as much a Friday Wuss as the students-of-today.

In my day, quoth I, in the last century, in TCD, we worked a full week. In UCD, the 1970s, otoh they had classes on Saturday morning. I knew this because while I was doing 1st Science in TCD, The Beloved was enrolled in 1st Arts in The Other Place UCD. I usually went out there for the 10am English lecture which was on her schedule. I learned a lot about 20thC English Literature. On one memorable occasion Dennis Donoghue and Augustine Martin did a two-hander on Waiting For Godot first playing it portentous and then playing it for larfs. It was pretty funny but also a useful insight into diversity and inclusion. Neither way was right, yet they clearly conveyed  quite different messages from exactly the same text. It's the kind of implicit lesson that makes a University education worth something. I would never have had that experience if I'd thought classes were a chore that kind of got in the way of hammer-time studenting.

Woefully, fatally, The Institute requires us to take attendance at every class. Attendance! for adults! who are paying fees, eligible to vote and probably paying taxes from their weekend jobs. If the stuff we taught was any good, the students would be knocking on the door to hear what we had to say, or get access to the stimulating scientific experiments in which we were giving them the chance to participate. haaaaaaRUMPH!

Sunday, 12 January 2020

Sunday Mixum

Don't have TV at home so have not had footage of the Australian wildfires in my face. So I checked in OzzyMan [usually a fast-talking ironic funny sort of bloke] on the woeful [as in shit] response of the Australian central government to the crisis. From which I have lifted the trib [pic above] to ordinary back-country firemen. Other stuff:

Saturday, 11 January 2020

Pizzagate Chronicles

We live on the Northside . . . of a valley in The Blackstairs, a range of hills in the Sunny South East of Ireland. To call them mountains would be a great exaggeration. Living on the Northside means that we catch all the sun, if any, which makes a big difference in the Winter. Our fields get defrosted by lunchtime, while it is still white across the shady side of the valley. Because we live there and can go any time, we rarely go up into the hills except to Bo-Peep our sheep. And almost never go trekking on the farside hill tops we see from our kitchen window. 10 or 12 years ago, The Boy was home and nothing would satisfy him but that he take his two teenaged sisters, Dau.I and Dau.II, camping. There is a gap of 18 and 20 years between him and them. One afternoon, accordingly, they packed a tent, sleeping bags and some iron rations into rucksacks and set off on their adventure.

As it happened I had a big batch of bread-dough a-proving in the kitchen and nothing would satisfy me but that I make and deliver <surprize!> a stack of pizzas. Part of the motivation was that I had recently bought an ALDI pizza tray rack set [L]. If not now, when . . . I asked myself. The thought being the deed, as tea-time was falling, The Beloved and I hot-footed up the rough pathway from the roadway and cried "PizzaaaH delivery!" until a faint cry located our offspring as they were thinking of eating apples and granola bars for their hard-chaw dinner.

Since then someone has installed a sheep-proof wicket gate where the access path meets the road. On the first Saturday of the year, The Boy was visiting again and nothing would satisfy him but that he went for a walk up to Caher Roe's Den, one of the peaks hereabouts. Everyone else was too full of mince-pies to join him but Gdau.I generously lent her Dad her woollen gloves: against him being benighted on the hill by descending fog. He returned in good order 4 hours later just as we were leaving in the car to go ho-ho-ho a-wassailling at a neighbours' gaff. The Boy was wet to the knees and in need of a hot toddy. "Damme, I've lost one of the gloves. It must have fallen from my pocket when I took out my water bottle. Could you check between Pizzagate and the road?". Pizzagate!? Clearly our delivery of hot pies had made an impact . . . on the toponymy of the Blackstairs.

After we'd consumed all the canapés at our friend's gaff, we detoured to Pizzagate and I jogged up the pathway looking for the orphan glove only to encounter two walkers who were in the process of hanging it nearer to eye-level on an out-poking twig. "I'll have that" quoth I, "and thank you for the trouble". We fell to talking while admiring the view and I established where we lived on the far side of the valley. "Do you still play the saxophone?" one of the lads asked. At which I must have looked completely bizarred because it seemed to be utterly random. "I walked past your place 8 or 9 years ago, and someone was in the yard playing the saxe, or was it a trumpet". That wasn't me (of course) but was very likely to be Dau.II who acquired a Saxe aged 15 and tootled away for the next several years. Living in a block of flats in central Cork has inhbited her practice, I am sorry to report: but the cakes are still mighty.

Friday, 10 January 2020

Ripping out pages

I've more less resolved to stop buying books. The National Library Service allows you to source any book you want, so long as there is a copy in the country. You can order it on line, have it delivered to any branch of any county library, and return it [when you're good and ready!] to the same place or any other branch in the Republic. With Dau.I working for head office in Dublin City Library, I have a mole in the system and she will often order books which she thinks I'd like and have them ready for collection in Tramore or Bagenalstown - the two libraries I pass most often.

It wasn't ever thus. In the 1960s and 70s and 80s it was, to say the least, inconvenient to get a read of a particular book with buying it. And I stopped buying new books when I discovered Yard Sales in our Boston years: perfectly serviceable reading matter could be had @ 25c for paperbacks and 50c-$1 for hard-covers. Second-hand books acquired their own quirky attraction: I developed a taste for nautical non-fiction from before WWII and that bled into the quirky, funny, short stories of WW Jacobs. To the nearest whole number, nobody reads Jacobs any more and I'm reluctant to clear them out as unread clutter [which they are] lest they go straight to pulping as unsellable at any price. Yard-sale books also have the virtue of serendipity: random collections yield some unexpectedly delightful surprises.

Somewhere along the way I bought a really ratty 1913 copy of Jock of the Bushveld by Percy Fitzpatrick. Every page had little line-drawings in the margin and the 2 dozen full page illustrations were all present. My intention was to make ironic postcards from the illustrations and cut out the line drawings of animals and assegais and make them into a collage of Victorian imperialist sentiment. But I couldn't bring myself to cannibalise the book in this way and eventually I restored it to a good reading copy during my book-binding days in the mid-1980s. I've never read it, but it's the sort of quirk that I might try reading aloud to my grandchilder next time they're visiting. If they start to fidget I can always switch to Paddington Bear or Roger Lancelyn Green which are not quite so retro.

When the Beloved went to college in 1973, she opted to read French and Arabic [it must have been the heritage calling] and her Arabic tutor was an orientalist called Dr David James. I met him a couple of times before The Beloved embraced motherhood to the exclusion of studenting: he seemed a nice, kindly, youngish, bookish sort of bloke. He passed out of our ken as passing teachers do. He appeared suddenly in the news nearly two decades later when we'd returned to Ireland after sojourns in USA and UK. It transpired that he'd secured a job as curator of oriental manuscripts at the Chester Beatty [R] Librarynot just the best museum in Ireland but one of the best in Europe’. Much as he treasured the gorgeous collection, he treasured money more, and took to c a r e f u l l y cutting out illustrated pages from oriental books and selling them to rich people who wanted exclusive use of  of these beautiful pictures. One of these looters-by-proxy sold on their acquisition to someone else, who wanted to get the picture appraised and the appraiser knew s/he'd seen the [effectively unique] picture somewhere before. Chester Beatty carried out an audit and Dr James went down. I'm glad I'm a low-maintenance sort of guy because my sketchy moral compass [forger] might have led me down a similar path if I'd needed the money.

Here's another ca$e of academic$ getting $educed by the eye-watering prices that wealthy people are prepared to pay for unique trophies. Once Richie Richboi got the fit young wife, the yacht, the mansion, the beach "hut", and a share of a Learjet, he starts to cast around for something - anything - that nobody else has. Christ's toenail; a scrap of the Gospel of St Mark; previously unknown poetry by Sappho; Jimi Hendrix's third best guitar; Monica Lewinsky's dress <eeeeuw>; 1935 Irish 2d coil stamp; the head of Francis Drake as baby. The rule of thumb appears to be price is inversely proportional to the utility of the object.

Thursday, 9 January 2020

Caesar's wife

Julius Caesar divorced his wife Pompeia in 63 BCE because she had been present when a lusty young patrician Publius Clodius Pulcher sneaked into her residence dressed as a woman with the intention of seducing the Great Man's missus. Despite there being no evidence of wrong-doing by Pompeia, Caesar divorced her, according to Suetonius "Quoniam meos tam suspicione quam crimine judico carere oportere" = because my family must carry themselves above suspicion let alone caught in criminal conversation. Clodius was murdered by an agitator political rival call Titus Annius Milo about 10 years later. Cicero defended Milo in court with a splendid piece of rhetoric Pro Milone which was widely distributed and continues to plague Latin students who are required to read and translate the 2000 y.o. polemic.

A  couple of scientific sketchiness stories surfaced since New Year. Here is one:
Only one of the three people in the montage above has won a Nobel Prize in the last couple of years. One of them, under implicit pressure to deliver, found an interesting result in the lab shared it with their line-manager, who presented it to the Boss. The three of them wrote up the story, and sent it in to Science - the premier US peer-reviewed general science journal - where it was quickly published. It helped that one of the authors had a Nobel gong. That happened nearly a year ago and was presumably a cause for celebration in the lab. Over Christmas they must have wanted to do a follow-up or something, but found that ". . . the results were not reproducible, and the authors found data missing from a lab notebook".  You can, with 20/20 hindsight, play spot the perp among the LinkedIn mugshots above if you are judgemental; but to me they all look within the normal range. Then again attributes like ethical compass, carefulness, attention to detail don't leap out from a pixellated passport photo.

What to do? What would you do?
  •  You could hope that nobody would notice: the presentation of the data [even if made up] were internally consistent enough to convince the editors at Science and 2 or 3 independent referees, after all. The results had the ring of truth. 
  • Or you can 'fess up, call Science and ask them to retract / suppress the paper. The Boss chose the latter, honest, option with a tweet (and an awkward phone call to Science) "I was a bit busy when this was submitted, and did not do my job well".
That's nice because it shoulders some of the blame for the debacle rather than throwing the most junior member of the trio under the bus. The trouble is that everyone at the top of my profession is way too busy for mental health and ethical integrity to flourish. Scientists do not grow to fill their lab-coats if the boss is unable to trust them to deliver. The technology in the lab has probably moved on so that the Boss probably could not work the kit themselves, so they have to delegate. And success in science accrues to those who can recruit a few good pairs of hands to do the lab-work, while the Boss applies for more money to keep the waggon rolling; presents their latest findings on the international conference circuit. Any big successful Nobel lab will also have a layer of middle managers = post-docs to whom is delegated the writing of papers and grant applications [at least early drafts] and supervision of beginners. Those persons have a key role in training and setting standards in the lab and are surely normally distributed as to ability and effectiveness even after two science degrees and several-to-many years of experience.

Who feels crap now?  Well all three of the faces above. The two junior people probably don't have a career in science anymore, so that's a bummer. For the Boss, there are no sanctions for did not do my job well and eeee but we do love a Nobel Prize winner. From Twitter, all the responses I saw were positive and supportive - shucks that's tough, I'm sorry for your troubles - rather than condemnatory. The editor and the referees who midwifed the miscreant Science paper should be feeling crap too because they were too credulous and blinded by the glitter of the Nobel Prize. But I doubt if there are any sanctions for them, either.

And what's all that lead in about Pompeia about?  Getting a Nobel Prize is not quite random, but there are lots of contributors who don't make the cut. Jocelyn Bell Burnell, for example. But having got the gong, life gets dialled up a notch. Not necessarily easier, but people listen to you even if you're being daft or cranky [Linus Pauling] ; you get a lot of free gigs and inhabit a lot of hotel suites. You owe it to the people who are fêting and feeding you to be above suspicion.