I think I'd be correct in stating with confidence that "all readers of The Blob desire to do good". Even if the grandson of Josef Mengele is tuning in from his fastness in the Paraguayan jungle, a case could be made that Opa Josi firmly believed he was carrying out important medical research. If we're going to Good, there's no point in piffling about at the fringes; we should aspire to do the most good possible with the resources that are available to us. A smart young chap called William MacAskill is making waves in plunging towards this goal of quantifying altruism. He's got his own website and and is now a Fellow at Emmanuel College Cambridge and also an associate professor at Lincoln College, Oxford. He's just published a book Doing Good Better: Effective Altruism and a Radical New Way to Make a Difference, which is comprehensively reviewed by Amia Srinivasan in the LRB. You should read it, ideas are developed there that I don't touch on here. MacAskill, is a disciple of Peter Singer an experimental ethicist who has forced us to think about the utility of compassion. Singer is fond of pointing out that we would happily ruin a $700 suit wading into a muddy pond to save a drowning child but won't shell out $7 to immunize one on the other side of the Third World.
Last Summer I confessed to being a Naive Utilitarian, with similar trepidation as people who admit to supporting a rubbish soccer team (Arsenal springs to mind) or liking the music of Blur. I've also filled The Blob with examples of quantification and statistical analysis with no more existential justification than that if numbers are there then they deserve to be analysed. Therefore I am predisposed to like an attempt to quantify or optimise an ethical issue like altruism or effective giving. But I also know that ethics is hard (having failed the Ethics Quiz) and that a superficial analysis of altruism is going to be annoying. Worse than annoying, because it's going to queer the pitch for other would-be rationalists.
Amia Srinivasan has digested enough of MacAskill's book so that I don't feel a burning need to run off and buy it. But if any close family member is stuck coming up to Christmas ...? MacAskill and another Oxbridge philosopher Toby Ord have pledged to cap their income (at about £20K) and give the rest to charity for their entire working life. Ord has founded Giving What We Can while MacAskill has launched 80,000 Hours which is about what your paid working life will be if you survive to 65. GWWC has apparently raised $400 million in pledges since its launch six years ago. But we all know that some charities deliver more of your cash to the deserving than do others. When Sinclair Lewis won the Nobel Prize for Literature in 1930 he pledged to donate the money to “a well-known young American author and his family, to enable him to continue writing” [himself]. You can check out a number of meta-charities like Give Well to see who has the fewest 4x4 vehicles and desk-bound fund-raising VPs. Forbes sorts US charities on the basis of charitable commitment [how much of your $$$ goes to Africa] and fundraising efficiency [how much it costs to get your $$$]. So that's one element of efficient giving.
But the impact of your $$$ can also be quantified. All your money can be given to ensure that every child in Africa has a pencil with which to get educated OR you can stop any child ever again being infected with hookworm Ancylostoma duodenale. You're too late to do that for smallpox, we've done smallpox. This is where QALYs quality-adjusted life years come in. I mentioned the idea in connexion with hepatitis back in July. QALYs are useful for allocated resources among competing claims on a finite cash-pot. Is it better to make triple-bypass heart-surgery available to all at government expense or build gyms in every school in the country (and ban the sale of cream-cakes)? You can do research to find out how much the quality of life is improved over how many years by these two alternative interventions and then make an informed allocation at budget time. The example in the LRB review says that life with AIDS is so grim [with constant infection and weird tumours popping up every third Thursday] that your QALY is 0.5 compared to happy healthy me with a QALY 1.0. Giving antiretroviral therapy can a) extend life expectancy but also b) crank up that QALY to 0.9. There are all sorts of problems with QALY - like having to ask Jo[e] Patient how s/he feels having contracted condition X rather than using an objective criterion. For example, people actually on dialysis rate their well-being higher than people who merely imagine being in the hospital getting filtered twice a week. Having established your QALYs, scaling up to the whole population is only elementary maths.
What we want to avoid is decisions being made, consciously or unconsciously, by fat old white men who want to get re-elected. We also want to avoid damn-fool ideas like buying expensive/glamorous pieces of kit or opening [requires Minister, ribbon, scissors, constituents and the press] new state-of-the art centres-of-excellence rather than dribbling out the money in unsexy but highly effective initiatives . . . like breakfast clubs for dirt-poor children. I think QALYs work if you are an uncorrupt government whose brief is to maximise the well-being of The People. It is pure greatest good for the greatest number utilitarianism in the tradition of Jeremy Bentham and John Stuart Mill. But it requires The Man to be as sternly uncompromising as any stoic Roman consul ordering the death of his own son.
Showing posts sorted by relevance for query QALY. Sort by date Show all posts
Showing posts sorted by relevance for query QALY. Sort by date Show all posts
Sunday, 4 October 2015
Thursday, 14 November 2019
Battens
I've been a bit of a fan of Jacob Rees-Mogg and John Bercow because they have made parliamentary democracy less dull across the water in London. I was therefore interested in the valedictory remarks of JRM about JB when the latter ended his decade as Speaker of the House. I knew it would be erudite and witty, and respectful because good manners is important to people like that. I was surprised when Rees Mogg claimed that the principal function of parliamentarians is to seek redress for the real or perceived the real wrongs of their constituents. Whoa Jake, what about steering the ship of state? keeping checks on the current government? making sure that legislation is fair and fit for purpose?
ReesMogg was alluding to his campaign to override the evidence-based decision of the National Health Service to not pay for Brineura, an extremely expensive therapy for a rare [maybe 40 cases in UK, 4 in Ireland?] neurological condition called Batten's Disease from which one of Rees Mogg's constituents suffers. All those with Batten's Disease are young because it is invariably fatal within 3 decades of being born. It is rare that any of them get to vote, either because of death or because a catastrophe of seizures, decline in speech, loss of mobility, involuntary muscle spasms, progressive dementia and visual impairment all conspire to make voting the last thing anyone in that home cares about. Batten's is a lysosome storage disorder brought about by a deficiency in one of the several dozen enzymes that do their work in those tiny sub-cellular blobs. I wrote a tutorial / Exec Summ about the various therapies that are coming on stream to alleviate the perfectly dreadful symptoms of some of these conditions.
It's big ask: science has to deliver a replacement enzyme to most of the cells in the body, encourage it through the cell membrane and then through the lysosome membrane without getting waylaid, degraded or misdirected. Actually, in the case of Batten's the drug of choice, Brineura, is delivered by a syringe-pump through a catheter direct to the middle of the child's brain. The mechanism is [obviously?] permanently attached, with a new cartridge of Brineura clicked into place as required like toner in a printer.
And for why? So that a tiny number of tiny people can have a fairer chance at a longer, fulfilling, pain-free, uncompromised life. That's really worthy, who wouldn't want that for a child? But these therapies are still quite hit-and-miss and never as good as a fully functioning natural gene making just enough of the right enzyme to work its clean-up magic.
Let's first guess the bill for the R&D. The road to develop a successful product is paved with mis-fires, dead-ends, failures and hair-tearings. Drug development costs are rocketing skyward, currently estimated on average to be $2,600,000,000 which needs to be recouped from each product that finally passes through the FDA and EMA [European Medicines Agency] approval process to The Market. That is the R&D cost, but The Market has to satisfy the manufacturing, marketing and distribution costs; the desire for profit; and the venture capitalists want a return on their investment. So BioMarin, the Pharma company that owns the intellectual property and the licence-to-sell, has a shit-ton of investment [$700million last year] that needs to be recouped . . . across a very small select market. Maybe 10,000 kids with Batten's in the whole [paying] world - excluding all the Battenistas who are born in the third world with no hope at all of paying for the therapy. The equation
But there have to be some standards before tax-payers foot the bill for medical interventions. In the UK the gate-keepers on payment are NICE National Institute for Health and Care Excellence. That's quite different to the EMA which keeps tabs on the safety and effectiveness of drugs. It's three tier in an ideal world:
Where does Jacob Rees-Mogg get his oar into the story? Well, one of his constituent (a young chap called Max Sewart) has Batten's and, in July 2019, the Mogg was able, with Speaker Bercow's imprimatur, to secure parliamentary time to urge the Health Minister and the NHS to come to any agreement with BioMarin that would supply Brineura to his constituent. His speech was peppered with numbers but is essentially an emotional appeal to secure preferential treatment for His Boy. I also know a very nice boy, currently in a horrendous spiral of destruction, addiction, self-harm and court-time who could really benefit from a few hundred €uros worth of support, evaluation and treatment. Without it, I fear that he'll be damaged beyond repair or dead before young Max. But that's the un-sexy end of health care provision, though, so Minister Simon Harris ain't going to break the rules on that story.
This essay draws a parallel between the negotiations with BioMarin over Brineura and Vertex over Orkambi, the cystic fibrosis which was approved in Ireland by Simon Harris, the Populist Health Minister, over and against the advice of experts and officials in his own department. Rees-Mogg and Harris will probably benefit in the polls for these preferring shameless appeals to emotive arguments rather than sober sifting of evidence, cost-benefit analysis and QALYs. One peculiar fact is that from the same data, some countries decide that a new drug will be paid for by the state; while other countries say no. QALY is an imperfect measure but at least it aspires, as does NICE, to be a fair and objective way of allocating the limited amount of money which the electorate is prepared to fork over in taxes. Brineura is approved for selling, though, and if Rees-Mogg really believes in Brineura, he may consider paying for young Max's treatment himself, hmmmmm?
ReesMogg was alluding to his campaign to override the evidence-based decision of the National Health Service to not pay for Brineura, an extremely expensive therapy for a rare [maybe 40 cases in UK, 4 in Ireland?] neurological condition called Batten's Disease from which one of Rees Mogg's constituents suffers. All those with Batten's Disease are young because it is invariably fatal within 3 decades of being born. It is rare that any of them get to vote, either because of death or because a catastrophe of seizures, decline in speech, loss of mobility, involuntary muscle spasms, progressive dementia and visual impairment all conspire to make voting the last thing anyone in that home cares about. Batten's is a lysosome storage disorder brought about by a deficiency in one of the several dozen enzymes that do their work in those tiny sub-cellular blobs. I wrote a tutorial / Exec Summ about the various therapies that are coming on stream to alleviate the perfectly dreadful symptoms of some of these conditions.
It's big ask: science has to deliver a replacement enzyme to most of the cells in the body, encourage it through the cell membrane and then through the lysosome membrane without getting waylaid, degraded or misdirected. Actually, in the case of Batten's the drug of choice, Brineura, is delivered by a syringe-pump through a catheter direct to the middle of the child's brain. The mechanism is [obviously?] permanently attached, with a new cartridge of Brineura clicked into place as required like toner in a printer.
And for why? So that a tiny number of tiny people can have a fairer chance at a longer, fulfilling, pain-free, uncompromised life. That's really worthy, who wouldn't want that for a child? But these therapies are still quite hit-and-miss and never as good as a fully functioning natural gene making just enough of the right enzyme to work its clean-up magic.
Let's first guess the bill for the R&D. The road to develop a successful product is paved with mis-fires, dead-ends, failures and hair-tearings. Drug development costs are rocketing skyward, currently estimated on average to be $2,600,000,000 which needs to be recouped from each product that finally passes through the FDA and EMA [European Medicines Agency] approval process to The Market. That is the R&D cost, but The Market has to satisfy the manufacturing, marketing and distribution costs; the desire for profit; and the venture capitalists want a return on their investment. So BioMarin, the Pharma company that owns the intellectual property and the licence-to-sell, has a shit-ton of investment [$700million last year] that needs to be recouped . . . across a very small select market. Maybe 10,000 kids with Batten's in the whole [paying] world - excluding all the Battenistas who are born in the third world with no hope at all of paying for the therapy. The equation
investment < cost per dose * life-expectancy-on-drug * # patients
yields the marketeers from BioMarin a figure of $£€500,000/yr for each customer. Even in the [paying] world that is more than any family dependent on a salary can pay. So the tab has to be picked up either by an insurance company or the Government.But there have to be some standards before tax-payers foot the bill for medical interventions. In the UK the gate-keepers on payment are NICE National Institute for Health and Care Excellence. That's quite different to the EMA which keeps tabs on the safety and effectiveness of drugs. It's three tier in an ideal world:
- nobody can buy things which are harmful,
- you can buy things where the balance of good outweighs the accumulation of likely adverse side-effects if you can afford them
- The Man will buy them for you if NICE decides that the tax-payer is getting value for money
- 400 nurses on the wards.
- 4,000 hip replacements
- 20 MRI scanners
Where does Jacob Rees-Mogg get his oar into the story? Well, one of his constituent (a young chap called Max Sewart) has Batten's and, in July 2019, the Mogg was able, with Speaker Bercow's imprimatur, to secure parliamentary time to urge the Health Minister and the NHS to come to any agreement with BioMarin that would supply Brineura to his constituent. His speech was peppered with numbers but is essentially an emotional appeal to secure preferential treatment for His Boy. I also know a very nice boy, currently in a horrendous spiral of destruction, addiction, self-harm and court-time who could really benefit from a few hundred €uros worth of support, evaluation and treatment. Without it, I fear that he'll be damaged beyond repair or dead before young Max. But that's the un-sexy end of health care provision, though, so Minister Simon Harris ain't going to break the rules on that story.
This essay draws a parallel between the negotiations with BioMarin over Brineura and Vertex over Orkambi, the cystic fibrosis which was approved in Ireland by Simon Harris, the Populist Health Minister, over and against the advice of experts and officials in his own department. Rees-Mogg and Harris will probably benefit in the polls for these preferring shameless appeals to emotive arguments rather than sober sifting of evidence, cost-benefit analysis and QALYs. One peculiar fact is that from the same data, some countries decide that a new drug will be paid for by the state; while other countries say no. QALY is an imperfect measure but at least it aspires, as does NICE, to be a fair and objective way of allocating the limited amount of money which the electorate is prepared to fork over in taxes. Brineura is approved for selling, though, and if Rees-Mogg really believes in Brineura, he may consider paying for young Max's treatment himself, hmmmmm?
Tuesday, 31 May 2016
Elite treat
Malignant melanomas have ballooned in recent years, increasing 2-3% year-on-year among over-50s in the USA. Despite being riddled with the 'wrong' version of the various tumor-suppressor genes, the Irish did not much fall prey to this dread disease in times past: a) there isn't enough sun to get sunburnt b) bare flesh (even exposing the arms or legs) was frowned on my the moral-police c) naked bonking in hayricks never happened. It was a different matter entirely when a pale-skinned, red-hairs, freckly gasún or cailín went out to Australia. Wearing a hat wasn't part of their culture, sun-block hadn't been invented, and the sun beat down on them without pity. So melanoma was much more common in those emigrants than among their stay-at-home cousins.
Mr Crown's case was that Pembrolizumab a Merck product marketed as Keytruda, would save the lives of some dozens of Irish people whose got to treatment for Mal Mel too late, or had bad genes or bad luck and are now at late-stage metastasized melanoma for which the prognosis is very poor if left untreated. Crivens, it's saved the life of 91 y.o. ex-President Jimmy "Guinea-Worm" Carter [prev]. Indeed prognosis is effectively a synonym for curtains and that patient will almost certainly become one of this year's crop of 140 people scythed to the grave by this disease. Pembro [we're on first name terms now] is super-elegant in its mode of action - it gees up the immune system to do its job more effectively.
With the consummate rhetorical flourish which we expect of consultants, senators and talking heads, Crown asked [I paraphrase] "What is the hold up, here? I have patients who have exhausted all other treatment options. The National Centre for Pharmaceutical Economics NCPE has made the calculations and given approval. Is it that politicians have been so prim about forming a government that there is no direction from the new Minister of Health?". I didn't know that we had a NCPE, let alone that it employs sixteen [16!] people. Nice work if you can get it but, like its sister quango the Food Safety Authority of Ireland FSAI [prev], there are no current vacancies.
What the NCPE do is some sort of QALY analysis [prev] to determine if the costs [$150,000 /yr!] of a course of treatment outweigh the benefits [another year's life for one person, and much glee among the sales department and share-holders in Merck]. I'm going to guess that, at a minimum, 140 people are in line to take up this drug before they join the crop of dead for 2017. Actually, it will be more because the oncologists will surely want to apply the treatment, which is demonstrably effective as early as possible after diagnosis. But let's be conservative here: 140 x $150,000 = €20 million. That's 60 affordable social-housing units for families which are currently sleeping on blow-up mattresses in a hostel for homeless men. But I only mention that emotive statistic because that's what The Media have been talking large about since the election . . . when they aren't talking emotively about Freeing the Water - we Freed the gays last year. YMMV, like one of those choose your own adventure books from the 1980s. Have tried the one called Realekonometrika?
Q. You have €20million at your disposal do you want to:
- Build 60 3-bed semis in outer Dublinia
- Buy another year of life for some red-headed over 50s
- Treble your money by depriving the haemophiliacs of their free Factor VIII
Wednesday, 13 July 2022
Let the children walk
My rant on Monday about cherish the children [♬ ♫ ♩ ♪] was an aside for today's update on SMA Spinal Muscular Atrophy a suite of inherited diseases which devastate a couple of dozen residents of Ireland and their families. Last time we looked at SMA, it was to showcase a new therapy Spinraza which could ameliorate the symptoms if a child was diagnosed early enough andif somebody would stump up €500,000 a year to inject the drug into the cerebro-spinal fluid 4x a year forever. The watchdogs of the public purse aka NCPE felt that we-the-people couldn't countenance such an outlay for so few beneficiaries. What galled me up a bit was that 12,000 people were prepared to sign a petition to persuade The Minister to over-ride the advice of his own experts but probably not able to stump up the actual folding money to achieve their started aim. It's the dilemma we all face whenever we bother to think about it: we'd rather spend the money on a) ourselves or b) on whatever is floating our boat this week rather than paying more taxes and letting the government make those decisions on our behalf.
SMA is in the news again because there is another petition to add SMA to the tests which are carried out on heel-prick blood-samples gathered at birth onto Guthrie cards [prev] and processed to early-detect progressive genetic diseases [including PKU, CF] for which therapies are available. Nope point in diagnosing conditions for which medicine has nothing to offer? This is a classic example of utilitarian thought, where you can, in theory calculate (QALY benefit of the therapy) ÷ (€€€€ cost of the therapy) and use this to decide rationally / fairly where a limited tax-take should be allocated. in 2019 NCPE said no to Spinraza. The additional cost to adding a tenth test to the existing Guthrie infrastructure is only €5 per heel or €300,000 a year to catch perhaps 6 de novo cases of SMA. Some EU countries already do this test.
It has been the holy grail of gene therapy to insert "good" genes into cells with "defective" genes and switch them on to work in place. My former colleagues [Hi Jane, Hi Pete] in Trinity College Genetics have been pursuing this dream to cure retinitis pigmentosa RP for at least 20 years. So far no patent [but plenty patients!], let alone a working product.
SMN the protein [structure R] is part of a complex which helps assemble another complex (the spliceosome) which processes genes into a final RNA form which can be translated into proteins. That sounds like an over-complicated I danced with a man of danced with a girl who danced with the Prince of Wales way of doing things; but in normal circumstances it works adequately. Evolution is about good enough, that will do rather than some perfectly crafted machina designed by deus. A single change Q136E in a single codon in the gene SMN1 prevents SMN the protein binding to ELAVL4 and so the first complex fails to come together and so (for want of a nail the kingdom was lost) cells, particularly some key motor neurons can't get their stuff together. But that Q136E lesion is just one of several ways in which SMN can go wrong: after all the protein is composed of 294 amino acids, any one of which has the potential to change. A111G, D030N are known natural variants which cause a milder form of neuromuscular degeneration known as SMA2. P245L and other changes cause SMA3 which is also rather less destructive of normal function.Mais revenons nous a nos Zolgensmas. Zolgensma was approved for use as an orphan (minority use for rare diseases) drug by the FDA on 24 May 2019 and the EMA on 18 May 2020. The Novartis blurb includes this telling disclaimer This press release contains forward-looking statements within the
meaning of the United States Private Securities Litigation Reform Act of
1995. Forward-looking statements can generally be identified by words
such as "designed to," "to halt," "hope," "can," "could,"
"possibilities," "potential," "leading," "excited," "milestone,"
"committed," "will,". I'd give a cynical chuckle at this point, except that my current take is that science has pulled a rabbit out of its hat this time. The fly in the ointment is that this single IV delivery costs €2 million. That's right on the cusp of what NCPE and their European oppos consider "worth it": 1 QALY being equal to €80,000.
Thursday, 1 December 2016
Orkambi - the state says No
Cystic fibrosis is a medical disorder inherited in an autosomal recessive manner. Autosomal means that CF is equally common in boys and girls. This is in contrast to the common forms of haemophilia [prev] where boys are more likely to have the condition because the relevant gene is carried on the X-chromosome. Girls have an extra X which can carry a normal gene and so compensate for the error on the other one. That is why some of Queen Victoria's sons and grandsons were bleeders but none of the princesses were. Recessive means that you need to inherit two duff copies of the gene to actually get the disease. That's interesting because it shows that so long as you have some active genes, even if only half the normal amount, you'll be grand, if not completely without symptoms.
That's the genetics; the maths indicate that, as about 1 Irish child in 1500 is born with CF, about 1 person in every 19 or 20 is a carrier of the disease. Carriers can also be found in other N European countries but Ireland takes the biscuit for the highest rate. If two carriers get [it] together, then 1/4 of their children will have CF; half will be carriers like their parents; and 1/4 will be clear. You could roll the dice twice and finish up with both kids affected. Why this works. As with Tay-Sachs, you can get yourself tested at the National Children's Hospital to see if you are a carrier. It's not worth it to check everyone but if your partner or you come from a family with CF running through it, it might be a good idea. One of the problems with the genetics and the testing is that there are several different ways in which the gene can be banjaxed. It helps to explain what the normal gene does.
We are tunnelled with mucus membranes: lungs, nose, sweat glands, vagina, vas deferens, gut . . . oh, and don't forget the pancreas. Wherever the body meets 'the outside' it tends to be wet and managing the degree of dampness is a key to keeping alighting microbes under control. One way to manage the lubrication of the mucus is to fit up epithelial cells with a channel that transports chloride ions across the cell membrane. Water will follow the chloride to equilibrate the concentration on either side of the membrane by a process called osmosis; as with cake-batter, more water = more runny.
This chloride channel is a bit of a mouthful: cystic fibrosis transmembrane-conductance regulator or CFTR to its friends. The R=regulator indicates that, as well as acting as a chloride channel, CFTR also controls the activity of other channels which shunt sodium about to balance the charge as well as the degree of dilution - sodium is Na+; chloride is Cl-.
The gene is in the nucleus of each cell, the CFTR channel [R] is, or should be, in the membrane, and getting the one to the other requires a few steps.
The problem is that there are at least 1000 mutations documented in CFTR which cause some degree of failure in the chloride channel. It's possible that you or I have a mutation in our CFTR gene that has so little effect that it will never be flagged unless Our Great Leader decides to sequence everyone's genome for our own good. T334W and T338I are flagged as 'mild', T334W means that 334th amino acid in the protein sequence, normally Threonine T has been replaced by Tryptophan W according to the conventional protein codes. By far the commonest mutation, responsible for about 75% of CF patients, is deltaF508 a deletion of a single amino acid at position 508. This is nothing to do with the channel itself [the hanks of 12 sausages shown embedded in the membrane at the top of the cartoon R]. deltaF508 rather has delivery problems because the absence of F508 makes the folding of the protein go wonk. The word on the street is that if you could ever get a deltaF508-CFTR inserted in the membrane it will function just fine.
A few years ago Vertex Pharma, a Boston based rational drug design company, launched a drug targetted at a particular CFTR mutation G551D - production=complete; a delivery=fine; channel=blocked mutation - called ivacaftor aka Kalydeco. The ball park figure for the cost of bringing a new drug to market (through a forest of trials, a blizzard of paperwork and multiple false-starts) is $1billion. The maths on G551D is that they make up about 4% of the USA's 30,000 CF sufferers. Those 1,000 people are being asked to pay $300,000/yr for the treatment. Vertex may start to show a profit on this revenue stream in the 5-10 years while the drug is still protected by patent. Obviously not every person with G551D will have health insurance or have multimillionaire parents. But this loss is offset by the market abroad. The drug makes you better than you were before because it allows a little chloride leakage but it's a long way from a cure.
A couple of years later Vertex went after deltaF508 with a different drug they called lumacaftor [who dreams up these wholly unmemorable tongue-mangling names? clearly not the marketing department] which was supposedly a chaperone which massaged the CFTR into something approaching normal shape. That prevents it being degraded and also help traffic some of the molecules to cell surface. You've got to reflect on the fact that the drug has to get from the gut into the blood-stream and thereby course round the body to the various epithelia. then it has to cross the cell-membrane to do its massage trick inside. lumacaftor is being marketed only in combo with ivacaftor under the name Orkambi. They can market it all they like in Ireland but the National Centre for Pharmacoeconomics NCPE has done the sums and advised against reimbursing the cost from the public purse.
Why? The spoil-sports! Well it's because the cost:benefit ratio doesn't stack up. Sorry to be so utilitarian about it. Possibly because there are more deltaF508s that G551Ds, the cost per year's treatment is 'only' €160,000. But, by one objective measure of lung function, the average Orkambi improvement compared to placebo is about 3%. The other measure preferred by NCPE and their other country equivalents is the QALY [multiprevs on The Blob]. The spokesman from the NCPE was on the radio Monday morning being blunt about matters financial; comparing the cost of supplying 700 people with this one, 97% ineffective, drug to the cost of building the new, and long promised, National Children's Hospital. That evening RTE gave a platform to a chap [the singular of data is anecdote] with CF who had responded extremely well to Orkambi. They quoted a tweet from the Health Minister who wants in an open letter to reassure CF Ireland that the analysis put out by the NCPE is "not the end" which suggests that objective, cost-benefit, QALY based decision-making can be massaged or discarded if it is politically expedient. He has instructed his Department to haggle with Vertex tp bring the price down. NCPE reckons €30,000 /year is the cost-benefit tipping point. But the pay-back time for the company on that price will be 25 years rather than 5 and the drug will be long off patent before the risk-taking venture capitalists have been paid back.
The chair of the NCPE only made his comparisons within the health service. But Ireland Inc. is brimful with blighted lives all of which could be made better with money
That's the genetics; the maths indicate that, as about 1 Irish child in 1500 is born with CF, about 1 person in every 19 or 20 is a carrier of the disease. Carriers can also be found in other N European countries but Ireland takes the biscuit for the highest rate. If two carriers get [it] together, then 1/4 of their children will have CF; half will be carriers like their parents; and 1/4 will be clear. You could roll the dice twice and finish up with both kids affected. Why this works. As with Tay-Sachs, you can get yourself tested at the National Children's Hospital to see if you are a carrier. It's not worth it to check everyone but if your partner or you come from a family with CF running through it, it might be a good idea. One of the problems with the genetics and the testing is that there are several different ways in which the gene can be banjaxed. It helps to explain what the normal gene does.
We are tunnelled with mucus membranes: lungs, nose, sweat glands, vagina, vas deferens, gut . . . oh, and don't forget the pancreas. Wherever the body meets 'the outside' it tends to be wet and managing the degree of dampness is a key to keeping alighting microbes under control. One way to manage the lubrication of the mucus is to fit up epithelial cells with a channel that transports chloride ions across the cell membrane. Water will follow the chloride to equilibrate the concentration on either side of the membrane by a process called osmosis; as with cake-batter, more water = more runny.
This chloride channel is a bit of a mouthful: cystic fibrosis transmembrane-conductance regulator or CFTR to its friends. The R=regulator indicates that, as well as acting as a chloride channel, CFTR also controls the activity of other channels which shunt sodium about to balance the charge as well as the degree of dilution - sodium is Na+; chloride is Cl-.
- The gene [DNA] needs to be translated into a full-length protein
- the protein needs to be trafficked to the membrane
- then it needs to open up for business and start moving chloride.
The problem is that there are at least 1000 mutations documented in CFTR which cause some degree of failure in the chloride channel. It's possible that you or I have a mutation in our CFTR gene that has so little effect that it will never be flagged unless Our Great Leader decides to sequence everyone's genome for our own good. T334W and T338I are flagged as 'mild', T334W means that 334th amino acid in the protein sequence, normally Threonine T has been replaced by Tryptophan W according to the conventional protein codes. By far the commonest mutation, responsible for about 75% of CF patients, is deltaF508 a deletion of a single amino acid at position 508. This is nothing to do with the channel itself [the hanks of 12 sausages shown embedded in the membrane at the top of the cartoon R]. deltaF508 rather has delivery problems because the absence of F508 makes the folding of the protein go wonk. The word on the street is that if you could ever get a deltaF508-CFTR inserted in the membrane it will function just fine.
A few years ago Vertex Pharma, a Boston based rational drug design company, launched a drug targetted at a particular CFTR mutation G551D - production=complete; a delivery=fine; channel=blocked mutation - called ivacaftor aka Kalydeco. The ball park figure for the cost of bringing a new drug to market (through a forest of trials, a blizzard of paperwork and multiple false-starts) is $1billion. The maths on G551D is that they make up about 4% of the USA's 30,000 CF sufferers. Those 1,000 people are being asked to pay $300,000/yr for the treatment. Vertex may start to show a profit on this revenue stream in the 5-10 years while the drug is still protected by patent. Obviously not every person with G551D will have health insurance or have multimillionaire parents. But this loss is offset by the market abroad. The drug makes you better than you were before because it allows a little chloride leakage but it's a long way from a cure.
A couple of years later Vertex went after deltaF508 with a different drug they called lumacaftor [who dreams up these wholly unmemorable tongue-mangling names? clearly not the marketing department] which was supposedly a chaperone which massaged the CFTR into something approaching normal shape. That prevents it being degraded and also help traffic some of the molecules to cell surface. You've got to reflect on the fact that the drug has to get from the gut into the blood-stream and thereby course round the body to the various epithelia. then it has to cross the cell-membrane to do its massage trick inside. lumacaftor is being marketed only in combo with ivacaftor under the name Orkambi. They can market it all they like in Ireland but the National Centre for Pharmacoeconomics NCPE has done the sums and advised against reimbursing the cost from the public purse.
Why? The spoil-sports! Well it's because the cost:benefit ratio doesn't stack up. Sorry to be so utilitarian about it. Possibly because there are more deltaF508s that G551Ds, the cost per year's treatment is 'only' €160,000. But, by one objective measure of lung function, the average Orkambi improvement compared to placebo is about 3%. The other measure preferred by NCPE and their other country equivalents is the QALY [multiprevs on The Blob]. The spokesman from the NCPE was on the radio Monday morning being blunt about matters financial; comparing the cost of supplying 700 people with this one, 97% ineffective, drug to the cost of building the new, and long promised, National Children's Hospital. That evening RTE gave a platform to a chap [the singular of data is anecdote] with CF who had responded extremely well to Orkambi. They quoted a tweet from the Health Minister who wants in an open letter to reassure CF Ireland that the analysis put out by the NCPE is "not the end" which suggests that objective, cost-benefit, QALY based decision-making can be massaged or discarded if it is politically expedient. He has instructed his Department to haggle with Vertex tp bring the price down. NCPE reckons €30,000 /year is the cost-benefit tipping point. But the pay-back time for the company on that price will be 25 years rather than 5 and the drug will be long off patent before the risk-taking venture capitalists have been paid back.
The chair of the NCPE only made his comparisons within the health service. But Ireland Inc. is brimful with blighted lives all of which could be made better with money
- ghetto-estates
- educational deficits, in the ghettos
- job prospects, ditto
- access to low-quality 'recreational' drugs, ditto
- suicides attempted and 'successful'
- years lost commuting in cars
- homeless people
- homeless people with addiction issues
- asylum-seekers lost in red-tape for a decade
- under-funded science
- Arts, Culture and the Gaeltacht
- exorbitant rents
- in crappy houses
- insufficient speech therapists
- obesity, fitness, food quality
- bachelor farmers
- sewage on beaches
Thursday, 31 August 2017
Bad luck
We live in a dog-eat-dog world. The worldview in Ireland, UK and USA, the three countries where I've lived for the longest time, is that you have to live your own misfortune . . . unless you have insurance. Even having paid life or health or house insurance for years, you can still get caught with your pants down because of the small print [which nobody reads] exclusions. In January 2010, our lane was washed away in a flood generated by 50mm of unseasonably warm rain falling on 30cm+ of accumulated snow. Snow packs 9 parts air to 1 part water. So that was a month's rain in a couple of hours, which amounted to 2-20 [hard to estimate the effective catchment] acre/feet of running water - which overwhelmed the drains. It had happened once before in the Summer of 1997, so floods hereabouts don't come regular like the monsoon but when they come they run. Nobody else seemed interested in repairing the lane so that we could drive to work or get to the doctor. Accordingly we had to spend about €2,000 in fill, digger-time and surfacing to restore access to the outside world.
Last Tuesday 23/Aug a similar amount of rain was dumped on the NW of our green isle, especially on the Inishowen peninsula and widespread flooding resulted. A chicken farm lost all its stock drowned, bridges were under-cut and collapsed, sinkholes appeared in the middle of roads, all the equipment of a boxing gym was washed out to sea and many houses had water in their living rooms. When things happen in more than threes, it is worth politicians making a TV appearance and forcing the minority government to free up some money to restore the status quo ante or at least compensate the people for their losses. Quickly too, please, families can't survive for long without dry bedding, a fridge and a kettle to make a nice cup of restoring tea. If we had prudent governments they would anticipate such untoward events and ring-fence an emergency fund. But no government hereabouts can see beyond the next election and survives by handing money out rather than taking money in against a rainy day. We spent the 'Pension Reserve Fund' during the crash. The British press, with an excess of chauvinism, talked about damage in Derry, just across the border. As far as they are concerned there in no weather [see map R] in the Republic; on in France for that matter.
Could be done better, or with more compassion, or with more equity. Then again, there are many people who now live in houses which should never have been built there. In the Boom, planning went out the window as developers acquired sites in flood-plains. built house, sold them, went bankrupt later. What should we-the-tax-payers do about that? Because, with flood insurance, the rule seems to be one strike and you're out of the net. In some cases, the government can put in some infrastructure: flood defense berms or walls: the Feds are putting loads of dollars into that round Yuba City California. But it has to be cost-benefit QALY effective. If it's cheaper to knock houses and build them further up the hill, maybe the government could swallow some of its market-driven, self-sufficiency dialectic and help with that. Well shucks and jimminy, they found $42 million in the 1980s to relocate the plain people of Centralia, PA when a subterranean fire made the town uninhabitable. If they can do it the land of the free, it can be tried elsewhere. Someone, preferably not a politician, has to make a call between bad luck and bad judgement.
The Inishowen event was apparently the tail-end of Hurricane Gert. Even as Gert was blowing out across N Europe, the next storm in line, Hurricane Harvey, was building in the Caribbean ready to deliver 1 m of rain to the coast of Texas . . . with added storm surge when the tides were coincident. That's 20x more rain than what overwhelmed the drains, roads and emergency services in Ireland last week but these things are somewhat relative. Yesterday I was, metaphorically, in Houston, looking at other deficits in forward-planning w.r.t. flood control and building houses downstream of the massive constructions that 500-year-storm flood control requires.
Could be done better, or with more compassion, or with more equity. Then again, there are many people who now live in houses which should never have been built there. In the Boom, planning went out the window as developers acquired sites in flood-plains. built house, sold them, went bankrupt later. What should we-the-tax-payers do about that? Because, with flood insurance, the rule seems to be one strike and you're out of the net. In some cases, the government can put in some infrastructure: flood defense berms or walls: the Feds are putting loads of dollars into that round Yuba City California. But it has to be cost-benefit QALY effective. If it's cheaper to knock houses and build them further up the hill, maybe the government could swallow some of its market-driven, self-sufficiency dialectic and help with that. Well shucks and jimminy, they found $42 million in the 1980s to relocate the plain people of Centralia, PA when a subterranean fire made the town uninhabitable. If they can do it the land of the free, it can be tried elsewhere. Someone, preferably not a politician, has to make a call between bad luck and bad judgement.
The Inishowen event was apparently the tail-end of Hurricane Gert. Even as Gert was blowing out across N Europe, the next storm in line, Hurricane Harvey, was building in the Caribbean ready to deliver 1 m of rain to the coast of Texas . . . with added storm surge when the tides were coincident. That's 20x more rain than what overwhelmed the drains, roads and emergency services in Ireland last week but these things are somewhat relative. Yesterday I was, metaphorically, in Houston, looking at other deficits in forward-planning w.r.t. flood control and building houses downstream of the massive constructions that 500-year-storm flood control requires.
Thursday, 14 March 2019
Caring
I am fond of intoning that Science is A way of knowing. Because I know that a lot of things that matter can't be measured; while many things that can be measured don't matter. Indeed the current obsession with measuring a record keeping can have a net negative effect on productivity. I left work last night (at 1704hrs) with our chief technician, for example, but she had to clock out with her work ID card as she left the building. Not me, I'm
Science's way of knowing is to measure stuff and assemble evidence to make sense of the world. The spirit of the times is that only STEM is productive for the economy; none of those Arts-Block degrees are actually going to create jobs or swell the government coffers . . . so they're useless. This week is Research Week and there was a speed-dating session for researchers from the Two Institutes in the regions that the govt is trying to force into an arranged marriage. Shamefully they asked the contributors to prepare a 10 minute presentation and then, overwhelmed by subscribers, cut the time down to a rigidly chaired 5 minutes. Rigid chairing is generally A Good Thing: stops the class bore from droning on and on. But 5 minutes is rather disrespectful of any research that isn't wholly superficial. Ho hum, maybe the twitter soundbyte, low-attention-span, generation is now the new normal. And, I'm afraid to say that several of these fishing for interesting collaborators talks would have been unengaging if they'd gone on for another 30 seconds.
But one researcher shilling for someone to talk to; and maybe collaborate with, was interested in caring, how to, in the best possible way. Her interest started in her mother's head when the older lady suffered a disabling stoke . . . and the speaker became her mother's primary carer . . . between the initial trigger in 2005 and the old lady's death in 2012. That's seven years of increasing dependence and closeness that was by this account pretty intense, generally exhausting and mostly positive. Less reliably positive was the couple's interaction with other people, protocols and institutions. A couple of years after her mother's death, Our Carer encountered an acquaintance whose mother was demented and wondered "how would our experiences compare?". From that question a research project was born
- find a way to reliably capture the experience of patients and their carers
- assess what adverse and positive events had greatest impact on the well being and QALYs [prev] of the patient and the equanimity of the carer
- calculate what changes in professional practice would cost the least to have the most postive impact on the experience of 'receivers of service'
- implement these changes until the money runs out
- assess whether the changes do actually enhance the well-being and QALY-longevity of patients on their final run.
Hard to reliably measure happiness and well-being; and QALYs are in a sense an assault on the lived experience of sick people. But being a bit fuzzy doesn't mean that these "outcomes and deliverables" are not worth striving towards.
Tuesday, 5 February 2019
Safety in the workspace
You can only die once but you can do damage to yourself so many times: ah the pain, the pain; I wish I hadn't done that. Sawing through my thumb as well as a 10cm Wavin pipe. Immersing myself in a vat of paint-stripper. Immersing my arm in a vat of pirhanas. Standing in the way of a txtn car driver. Splashing radioactive phosphorus in my eye. The feedback on these actions was more or less immediate - at least I knew I'd done something foolish at the time. Because the hazards were known knowns. Back in the day we used to pipette-by-mouth = suck up a precise amount of liquid into calibrated tube and run it into glass beaker: urine, phenol, microbial cultures . . . And I don't think that safety-glasses were A Thing in the 1970s. I spend much of my time in the lab at work now reminding students to put their safety-glasses, like, in front of their eyes.
I came through my road-traffic accident damaged but unbowed, although my bike didn't. The phosphorus in the eye maybe not so much: I'm still expecting a tumor 30 years later, although I can't even remember which eye took the hit. Which brings me to Canadian artist Gillian Genser who didn't want to handle any of those narsty man-made artifical things; she only dealt in natural products like mussel Mytilis edulis shells from which she crafted eerie amazing sculptures [R her Adam's muscles are made of mussels, geddit]. It took weeks and weeks of work and after some time on the project she started to feel ill: puka-puka, headaches, cramps. In Canada, a civilised country, if you fall sick then you get referred to [a succession of] medical specialists without having to sell your house. "When they asked me if I worked with anything toxic, I said no, that I only used natural materials". 15 years after adverse symptoms first started, she twigged (seemingly without much help from the medical consultants) that she had been inhaling mussel dust that was loaded with arsenic and cadmium because the invertebrates were grown in the South China Sea bathed in the industrial outfall from dozens of unregulated paint and plastic factories. That's what mussels Mytilis edulis and oysters Ostrea edulis do: they filter hundreds of litres of water a day accumulating minute frags of food and minute quantities of coliforms and heavy metals. Note the specific name for those shellfish edulis = edible. But maybe nowadays not so much. Irish water is still discharging raw sewage into Waterford Harbour right across the river from Woodstown oyster farm. Genser is still alive after 15 years of occupational toxicity but her QALYs are terrrrible.
I picked up this story from MeFi where, as ever, the commentary is at least as interesting and informative as the original story.
I came through my road-traffic accident damaged but unbowed, although my bike didn't. The phosphorus in the eye maybe not so much: I'm still expecting a tumor 30 years later, although I can't even remember which eye took the hit. Which brings me to Canadian artist Gillian Genser who didn't want to handle any of those narsty man-made artifical things; she only dealt in natural products like mussel Mytilis edulis shells from which she crafted eerie amazing sculptures [R her Adam's muscles are made of mussels, geddit]. It took weeks and weeks of work and after some time on the project she started to feel ill: puka-puka, headaches, cramps. In Canada, a civilised country, if you fall sick then you get referred to [a succession of] medical specialists without having to sell your house. "When they asked me if I worked with anything toxic, I said no, that I only used natural materials". 15 years after adverse symptoms first started, she twigged (seemingly without much help from the medical consultants) that she had been inhaling mussel dust that was loaded with arsenic and cadmium because the invertebrates were grown in the South China Sea bathed in the industrial outfall from dozens of unregulated paint and plastic factories. That's what mussels Mytilis edulis and oysters Ostrea edulis do: they filter hundreds of litres of water a day accumulating minute frags of food and minute quantities of coliforms and heavy metals. Note the specific name for those shellfish edulis = edible. But maybe nowadays not so much. Irish water is still discharging raw sewage into Waterford Harbour right across the river from Woodstown oyster farm. Genser is still alive after 15 years of occupational toxicity but her QALYs are terrrrible.
I picked up this story from MeFi where, as ever, the commentary is at least as interesting and informative as the original story.
- While everyone wants an inexpensive, disposable glove to use with acetone, there is no disposable glove that offers protection from it or any other chemical in the ketone class.
- "Which I did barehanded, because I was eighteen and indestructible".
- "Almost all cities in North America have lead contaminated topsoil thanks to the years of leaded gasoline use" Don't be growing tomatoes in that stuff!
- "Anybody else remember using their teeth as a child to crimp the lead split-shot weights onto fishing line?"
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
MKTFLILALLAIVATTATTAVRVPVPQLQPQNPSQQQPQEQVPLVQQQQFPGQQQQFPPQ
QPYPQPQPFPSQQPYLQLQPFPQPQPFPPQLPYPQPQSFPPQQPYPQQQPQYLQPQQPIS
QQQAQQQQQQQQQQQQQQQILQQILQQQLIPCRDVVLQQHNIAHASSQVLQQSTYQLLQQ
LCCQQLLQIPEQSRCQAIHNVAHAIIMHQQQQQQEQQQQLQQQQQQQLHQQRQQPSSQVS
FQQPQQQYPSSQVSFQPSQLNPQAQGSVQPQQLPQFAEIRNLALQTLPAMCNVYIPPHCS
TTIAPFGIFGTN
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
>A0A1P8DTE7_9POAL Alpha-gliadin OS=Triticum spelta
MKTFLILALLAIVATTATTAVRVPVPQLQPQNPSQQQPQEQVPLVQQQQFPGQQQQFPPQ
QPYPQPQPFPSQQPYLQLQPFPQPQPFPPQLPYPQPQSFPPQQPYPQQQPQYLQPQQPIS
QQQAQQQQQQQQQQQQQQQILQQILQQQLIPCRDVVLQQHNIAHASSQVLQQSTYQLLQQ
LCCQQLLQIPEQSRCQAIHNVAHAIIMHQQQQQQEQQQQLQQQQQQQLHQQRQQPSSQVS
FQQPQQQYPSSQVSFQPSQLNPQAQGSVQPQQLPQFAEIRNLALQTLPAMCNVYIPPHCS
TTIAPFGIFGTN
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
Wednesday, 29 August 2018
No booze is good booze
Mighty new study, sponsored by Bill & Melinda Gates, and published in the Lancet indicates a) the alcohol is detrimental to your health [no surprises there] and b) a tiny amount of alcohol is detrimental to your health. According to them, the only safe level of alcoholic consumption is no alcoholic consumption and the best solution (plonkodrain) for a healthy future is shown [L]. This is a bit unfortunate for those of us who like a glass of wine - to celebrate the end of a hard week at work, for example. We have been justifying this preference with the studies showing that moderate amounts of red wine can help reduce cholesterol-driven cardio-vascular events. Actually, if you live in The West [countries binned into High SDI Socio-demographic Index: the 5-point scale used in the Lancet study] there are "some protective effects for ischaemic heart disease and diabetes". But those wins on the swings are lost on the roundabouts of other adverse outcomes from our "only a small one" policy. For example, women's relative risk of developing breast cancer [UP] as a factor of drinks per day [Across]
Note: a 700ml bottle of 12% wine has about 65g of ethanol on board. 'Tis a long way from a case/control trial that chart was r'ared, though. Each dot is a country and the forest of vertical and horizontal bars are the associated errors of estimate, so the data on which the Clear Lancet Statements are based are really very noisy. "we estimated the dose–response relative risk curve using mixed-effects logistic regression with non-linear splines" doesn't really help me or my Uncle "Toper" Jim understand how the dots get their positions on the charts . . . and gives us a psychological out - "I'll be okay, there's no history of cirrhosis in my family".
And, contrary to the Headline take-home that NO alcohol is the only safe amount, their own Fig 5 [L] appears to bottom out at 1 unit a day. That picture is the executive summary of the whole meta-analysis of all the negative outcomes of drinking alcohol. The noise has been sanitised summarised by the grey trumpet showing that the variance increases as higher booze-rates are considered. The study is freely available and long, so if you are concerned you should do a keyword search through the full-text of the study to see the connexion between, say, alcohol and Russia: "mortality crisis in Russia is a striking example, where alcohol use was the primary culprit of increases in mortality starting in the 1980s and led to 75% of deaths among men aged 15–55 years". Lots of informative graphics in the paper but all qualified by the noisiness of the data.
I was interested to encounter a new term to match QALY Quality Adjusted Life Year [multiprev] which allows us to quantify the effects of, say, different treatments for cancer. DALY is a Disability-Adjusted Life Year (DALY) which in turn is the sum of Years of Life Lost (YLL) and Years Lost due to Disability (YLD). If you survive a year after your alcohol-induced ischaemic stroke but only 50% fit-for-function that's half-a-DALY. I [now] drink very little, because in Ireland it costs very much.
I was interested to encounter a new term to match QALY Quality Adjusted Life Year [multiprev] which allows us to quantify the effects of, say, different treatments for cancer. DALY is a Disability-Adjusted Life Year (DALY) which in turn is the sum of Years of Life Lost (YLL) and Years Lost due to Disability (YLD). If you survive a year after your alcohol-induced ischaemic stroke but only 50% fit-for-function that's half-a-DALY. I [now] drink very little, because in Ireland it costs very much.
Monday, 29 May 2023
Her lovely horse
For a few months in 2016, we had "Young Bolivar" aka A Good Pair of Hands staying /WWOOFing with us learning English. His last project was building a mighty, and mighty handy, woodshed at the bottom of the yard. We measured up and decided that for the desired design we'd need N=130 lengths of western red cedar Thuja plicata to clad the walls. Jim Davis in Graigcullen didn't cut to length and threw in a few extra planks for luck, so we were left with a big stack of surplus planks not to mention many offcuts of different lengths from 150mm to 900mm in length. Heck'n'jiminy that's seven (7) years ago! The cedar planks have been stacked at the back of the woodshed all that time, quietly drying out some more.
This Spring Dau.II would have nothing but that we build a tree-house for her niblings down in our sustainable micro-forest. That's as well as the refurbed garden seat. And, because cedar is naturally pest-resistant and because it was already on site, we robbed the stack in the woodshed to fabricate the base of the tree house.
Sunday, 11 October 2015
Updates 11 October
Surfing the standing wave [Vimeo 3:30 mins] No more bobbing about in the sea waiting for the wave and you don't need to shell out folding money to surf. Now you just need a wet-suit including neoprene gloves (because its cold out there ["groundhog"]) and surfboard and a river in spate conveniently close to a highway. While you're out off your sofa and allll wet you might go down Puerto Rico way for an arty Surfers vs Technologia film [Vimeo 6.25 mins] those dudes are carving some gnarly tubes.
Remember Primo Levi? And his brilliant book of sciency stories The Periodic Table? Well his Complete Works is out for a hefty price £56 / $63 until you reflect that it is >!3000!< pages in three volumes with a slip-case. Clearly the Christmas present for those who spell Oświęcim with the correct accents. The review / retrospective in the New Yorker is also worth reading. It reflects sensibly and sensitively on his accidental/suicidal end. While you're about it, read a short story Quaestio de Centauris by the great man?
Remember Hans Rosling talking about life expectancy and coffee-cups? This tells you to turn up on our mountainside for my burial shortly after 23rd July 2038. Obviously your mileage may vary but you're unlikely to do longer than me with a Granny who hung on till she was 108 and a Gt-granny on the other side who died at 103. And on the subject of death, I don't think I've posted about Years of Life Lost, YOLLs [3.15 min vox video] a sort of counter-QALY.
Alison Gopnik? What about a predictably radical critique of school-based education which Gonnik finds to be neither sufficiently persistent about practice-makes-perfect learning nor at all interested in real enquiry-based learning.
Remember the Royal Society and their recent desire to make videos about its connexions more widely available? I've just heard about a RS channel called Objectivity in which Numberphile filmista Brady Haran gets access to the Royal Society Library card catalogue. It's a channel so you'll have enough to keep you going while sporty people are watching Ireland and France play rugby this-arvo. What about hefting the standard yard and the standard pound? Super historic cool.
While I have your attention, I'll mention that, since 1988, 11 October has been designated National Coming Out Day. I guess that makes it LGBTQNCOD. Which is a bit of a mouthful. The Irish Examiner decided to interview Katherine Zappone and Ann Louise Gilligan whose Canadian marriage was unrecognised by the Irish Supreme Court in 2006. And HuffPo has some more nuanced advice on the pro & con of out.
Remember Primo Levi? And his brilliant book of sciency stories The Periodic Table? Well his Complete Works is out for a hefty price £56 / $63 until you reflect that it is >!3000!< pages in three volumes with a slip-case. Clearly the Christmas present for those who spell Oświęcim with the correct accents. The review / retrospective in the New Yorker is also worth reading. It reflects sensibly and sensitively on his accidental/suicidal end. While you're about it, read a short story Quaestio de Centauris by the great man?
Remember Hans Rosling talking about life expectancy and coffee-cups? This tells you to turn up on our mountainside for my burial shortly after 23rd July 2038. Obviously your mileage may vary but you're unlikely to do longer than me with a Granny who hung on till she was 108 and a Gt-granny on the other side who died at 103. And on the subject of death, I don't think I've posted about Years of Life Lost, YOLLs [3.15 min vox video] a sort of counter-QALY.
Alison Gopnik? What about a predictably radical critique of school-based education which Gonnik finds to be neither sufficiently persistent about practice-makes-perfect learning nor at all interested in real enquiry-based learning.
Remember the Royal Society and their recent desire to make videos about its connexions more widely available? I've just heard about a RS channel called Objectivity in which Numberphile filmista Brady Haran gets access to the Royal Society Library card catalogue. It's a channel so you'll have enough to keep you going while sporty people are watching Ireland and France play rugby this-arvo. What about hefting the standard yard and the standard pound? Super historic cool.
While I have your attention, I'll mention that, since 1988, 11 October has been designated National Coming Out Day. I guess that makes it LGBTQNCOD. Which is a bit of a mouthful. The Irish Examiner decided to interview Katherine Zappone and Ann Louise Gilligan whose Canadian marriage was unrecognised by the Irish Supreme Court in 2006. And HuffPo has some more nuanced advice on the pro & con of out.
Monday, 16 March 2020
The blind stay sane
All through the 00s, I worked in a Comparative Immunology lab trying to figure out why some cohorts of creatures got sick and others did not. We got through so much money trying to work out why Campylobacter was tolerated by the chicken's immune system but caused such a dramatic <bloooargh> reaction when we eat a dodgy chicken nugget. After years of talking about the idea, the lab started to work with Irish women who were exposed to HCV during the anti-D scandal but never got hepatitis. They must have had something special in their innate immune toolkit that blatted the virus before it could start reproducing. They [I'd left by then] tried to locate that p'arful magic because it would be really handy for developing new therapies against the condition . . . which resides in nearly 200 million people worldwide.
When Vice tells me that there are no cases of people born blind who are schizophrenic, my first response was to question the veracity of the statement. Because No cases seemed so unlikely . . . unless . . . it was a Venn Diagram intersection issue for two rare conditions: (rare x rare) might approach zero? That tasked me to learn what are those rates.
Schizophrenia is not uniformly rare: rates per country vary from 0.3% to 0.7%. That is a lot of people who need some form of care, attention or medication: 235,000 in Ireland. Compare that to rare like Batten's Disease [N = 4 in Ireland] or Cystic Fibrosis [N = 1,300]. Another way of looking at the impact per country is the DALY - disability adjusted life year; a metric clearly related to the QALY. This shows that schizophrenia is not so much fatal but that it does impact on the quality of your life. And the lives your carers and loved ones, although I'm not sure if / how that is incorporated in the following global view. Some untoward is happening in Indonesia and the Pacific islands while Europeans are less beset by schizophrenia.
Congenital blindness is much less common than schizophrenia. Something like 200 cases of born-blind children in Ireland from all causes. A small enough number that Goggin and O'Keefe (1991) could observe and interview almost all of them. It is really not unexpected therefore that we have no cases of blind schizophrenia in Ireland. There are insufficient numbers for the [dis]association to be statistically significant. Then again Ireland is a small country (1% of the EU population or 1/1000 for the whole world). If there are 20,000 congenitally blind EU kids, we expect 200 of them to be schizophrenic and there are none so there is a case to answer.
They say that we get 70% of our incoming information through the eyes and we process that weleter of photonic information down to manageable proportions. Visual illusions as well as being a staple for cchildren's quiz books, allow us to see / not-see the compromises the brain makes to make sense of the world out there. Psychologist RD Laing famously asserted that "Insanity - a perfectly rational adjustment to an insane world" and "Schizophrenia cannot be understood without understanding despair.". Maybe therefore, if you really damp down the incoming roil of conflicting information then you're less likely to be forced to compromise your sanity to make sense of it. Just think of irony - of which I am really over fond - where the meaning of the words is belied by the intonation or facial expression. Or picking up a lie or a false laugh by the subconscious processing of the other person's face.
Anyway it might make you reflect with wonder about the human condition - how things which we put quite confidently into different bins are actually unexpectedly entwined.
Via Mefi
When Vice tells me that there are no cases of people born blind who are schizophrenic, my first response was to question the veracity of the statement. Because No cases seemed so unlikely . . . unless . . . it was a Venn Diagram intersection issue for two rare conditions: (rare x rare) might approach zero? That tasked me to learn what are those rates.
Schizophrenia is not uniformly rare: rates per country vary from 0.3% to 0.7%. That is a lot of people who need some form of care, attention or medication: 235,000 in Ireland. Compare that to rare like Batten's Disease [N = 4 in Ireland] or Cystic Fibrosis [N = 1,300]. Another way of looking at the impact per country is the DALY - disability adjusted life year; a metric clearly related to the QALY. This shows that schizophrenia is not so much fatal but that it does impact on the quality of your life. And the lives your carers and loved ones, although I'm not sure if / how that is incorporated in the following global view. Some untoward is happening in Indonesia and the Pacific islands while Europeans are less beset by schizophrenia.
They say that we get 70% of our incoming information through the eyes and we process that weleter of photonic information down to manageable proportions. Visual illusions as well as being a staple for cchildren's quiz books, allow us to see / not-see the compromises the brain makes to make sense of the world out there. Psychologist RD Laing famously asserted that "Insanity - a perfectly rational adjustment to an insane world" and "Schizophrenia cannot be understood without understanding despair.". Maybe therefore, if you really damp down the incoming roil of conflicting information then you're less likely to be forced to compromise your sanity to make sense of it. Just think of irony - of which I am really over fond - where the meaning of the words is belied by the intonation or facial expression. Or picking up a lie or a false laugh by the subconscious processing of the other person's face.
Anyway it might make you reflect with wonder about the human condition - how things which we put quite confidently into different bins are actually unexpectedly entwined.
Via Mefi
Tuesday, 6 October 2015
QALYs for normal people
Two days ago I was on about utilitarianism and am naive enough to believe that governments can optimise the public good by rational decisions about who to tax and where to spend. But only by believing that all their citizens (black, female, blind, very small and very old included) are equal. QALY utilitarianism really doesn't work for individuals because we are all human. Even with my blunted affect I'm with E.M. Forster “If I had to choose between betraying my country and betraying my friend, I hope I should have the guts to betray my country.”. One of the theoretical bases of altruism is the concept of inclusive fitness: we'll make a sacrifice to benefit those with whom we have genes in common. JBS Haldane [previously] claimed that he would risk death by drowning to save two brothers or eight cousins: we'll naturally do more for our own children than a random black kid languishing in another country. And I'm mildly aggravated by people who manifest the Illusion of Control by trying to manage their lives/careers to achieve a specific goal. If you feel passionately about that goal then, almost by definition, you haven't subjected it to a cold rational cost-benefit analysis. If you want an internal debate about the morality of altruism, there is a longish piece in the Grauniad about giving money to strangers instead of spending it on [more] stuff for self. I'm afraid I flung it across the room: you can over-think things.
But hyper-rational MacAskill is not above offering life-coach advice from the perspective of one who is not close to being half-way through his. Here he speaks at TEDx to tell school- or college-leavers how they can best manage their lives if they have bleeding-heart tendencies. Taking a gap-year to go South and build huts for Africans is a waste of time and talent! You would do better to do one or more of the following.
But one final thing - take this advice with a pinch of salt. MacAskill accepts, with minor qualification, the idea that Norman "Short Wheat" Borlaug saveda billion many lives. I profoundly disagree. One thing that would help us all [I'm speaking for oaks and ants and oafs as well as Oxbridge graduates] is fewer people.
But hyper-rational MacAskill is not above offering life-coach advice from the perspective of one who is not close to being half-way through his. Here he speaks at TEDx to tell school- or college-leavers how they can best manage their lives if they have bleeding-heart tendencies. Taking a gap-year to go South and build huts for Africans is a waste of time and talent! You would do better to do one or more of the following.
- Become an entrepreneur or get up close to one. Entrepreneurs have to be generalists, so they upskill on a broad range of topics. The Beloved lucked into an office-help job with Clive Sinclair as the 8th hire at his ZX80 venture in Cambridge, UK. Two years later she was Customer Service North America in Boston, MA.
- Go into research. The market for researchers is under-supplied and the training is somewhat generic - if you can find out how a gene works you can find out whether compulsory Latin has benefit in primary schools or why dams fail. And you'll be able to discover where is the best place to dispose of your disposable income.
- Go into politics. Especially if you're at Oxbridge and have some rich friends: that cohort has a 1/30 chance of ending up in parliament.
- Upskill yourself. You'll be better off, and so will the poor, if you work for a year as an intern in a consultancy in Washington or Uppsala than if you wield a hammer in Ouagadougou.
- Get a job in Megacorp and climb the corporate ladder. You don't have to put all your earnings into cocaine and Porsches.
But one final thing - take this advice with a pinch of salt. MacAskill accepts, with minor qualification, the idea that Norman "Short Wheat" Borlaug saved
Tuesday, 28 July 2015
World Hepatitis Day
That would be today. I have enough on my calendar with Darwinday (12nd Feb) when I have been known to give donuts and Christmas when I have been known to give small presents to children. I am not about to starting giving people hepatitis at the end of July. Although I must confess that our sheep routinely and involuntarily share needles when they are being dosed for worms and vaccinated for contractible lambhood diseases. After a good bit of shifting about, Hepatitis Day has settled on 28th July because it is Baruch Blumberg's birthday. Baruch Whoberg? you may well say, but he was awarded the 1976 Nobel Prize in Physiology and Medicine for identifying the Hepatitis B virus in the blood of an Australian aborigine who was suffering from yellow jaundice. Jaundice is due to the failure to clear yellow bile through the bile-duct which can happen from wide variety of causes and can sometimes be treated with an intervention of quite elegant simplicity which saved the life of Pat the Salt in the week of his 90th birthday at the beginning of June. The treatment is so easy that it is possible to treat the whole thing as a bit of a joke "Who's the Chinaman seating on your sofa, missus", "B'godde Pat but you're the colour of your Sou'wester" but hepatitis in general is no joke at all.
Blumberg not only did the nifty academic identification thing to explain why one of his global patients was looking crook and feeling crap, he also went on to a) develop a molecular screen to identify blood donations that were infected with Hep B AND b) to develop a successful vaccine against that strain of virus. When that therapy was loosed on children, it reduced the rate of HepB infection among Chinese children from 15% to 1% within a decade. You can hardly begrudge Blumberg his Nobel for thus improving the quality of life of millions (a billion wouldn't be an exaggeration) of people across the World. Saving life and improving its quality is different from encouraging the increase in the human population and I've had occasion to slag the enNobeling of Norman Borlaug and Fritz Haber for causing the latter. On the slagging front, it is coincidental that Blumberg shared his 1976 Prize with Carlton Gadjusek, one of a handful of Nobelists whom I've met and who occasioned an ethical hand-shaking dilemma. On the small world front, it should be noted that Blumberg was educated in Far Rockaway High School seven years after Richard Feynman, another Nobel who has featured on The Blob. When Blumberg died in 2011 his boss stood up and said "I think it’s fair to say that Barry prevented more cancer deaths than any person who’s ever lived." Which give a clue about the grosser causes of jaundice. As an indication of liver failure, rather than a failure in the plumbing of the bile-duct, viral hepatitis can go on to cause complete liver failure, cirrhosis, liver cancer and death. As opposed to, say, small cell carcinoma of the lung which can rip through you and kill within months, hepatitis can make you feel increasingly terrible over years and years. If you believe in Quality Adjusted Life Years [QALY], ye durty Utilitarian, you'd surely upvote a cure for hepatitis when you come to allocate the cash within your health service.
15% of Chinese children is a helluva a lot of Hepatitis and that's only HepB. There are five identified Hep viruses named HAV, HBV, HCV, HDV and HEV. In evolutionary terms they are as different from each other as viruses can possibly be - some use DNA to deliver their message and others use RNA, for starters - but all have in common a tendency to settle in the liver and replicate there. Their replication, as with all viruses, involves infecting a cell, subverting the local nucleic acid replication machinery to make more virus, popping that cell to release dozen or hundreds of infective units to recursively repeat the process and propagate the virus. The viral propagation thus interferes with normal liver function which manifests initially as fatigue, nausea and other flu-like symptoms which get labelled as hepatitis when jaundice develops. The cirrhosis and liver cancer will develop in due course if you live long enough. Anita "BodyShop" Roddick, for example, died of a brain haemorrhage before HepC killed her. Roddick got her dose from a blood-transfusion but many of the other celebs who have a HCV infection in common, got it from shared needles - don't do your own tattoos, kids.
We all take our liver for granted until it goes wonk and then we begin to appreciate how many and how varied are its beneficial functions. I could have had a lot to say about HCV, because its investigation formed a key thread in the Comparative Immunology lab in which I worked for the first part of this century. But the Blob logs show that I have been unaccountably quiet on the matter. Will rectify this in the future because there are some ripping yarns to be told. But for today, take 5 minutes to reflect on the 180 million people across the World who suffer [sic!] from HCV infection. Of these half a million die each year, which puts it at almost the same level as the big killers malaria, tuberculosis and infectious diarrhoea. Nobody has a developed a vaccine against that cause of hepatitis at least partly because, like HIV, it is a RNA virus which mutates so fast that it is hard for any vaccine strategy to keep up. Lots of science done, more to do.
Blumberg not only did the nifty academic identification thing to explain why one of his global patients was looking crook and feeling crap, he also went on to a) develop a molecular screen to identify blood donations that were infected with Hep B AND b) to develop a successful vaccine against that strain of virus. When that therapy was loosed on children, it reduced the rate of HepB infection among Chinese children from 15% to 1% within a decade. You can hardly begrudge Blumberg his Nobel for thus improving the quality of life of millions (a billion wouldn't be an exaggeration) of people across the World. Saving life and improving its quality is different from encouraging the increase in the human population and I've had occasion to slag the enNobeling of Norman Borlaug and Fritz Haber for causing the latter. On the slagging front, it is coincidental that Blumberg shared his 1976 Prize with Carlton Gadjusek, one of a handful of Nobelists whom I've met and who occasioned an ethical hand-shaking dilemma. On the small world front, it should be noted that Blumberg was educated in Far Rockaway High School seven years after Richard Feynman, another Nobel who has featured on The Blob. When Blumberg died in 2011 his boss stood up and said "I think it’s fair to say that Barry prevented more cancer deaths than any person who’s ever lived." Which give a clue about the grosser causes of jaundice. As an indication of liver failure, rather than a failure in the plumbing of the bile-duct, viral hepatitis can go on to cause complete liver failure, cirrhosis, liver cancer and death. As opposed to, say, small cell carcinoma of the lung which can rip through you and kill within months, hepatitis can make you feel increasingly terrible over years and years. If you believe in Quality Adjusted Life Years [QALY], ye durty Utilitarian, you'd surely upvote a cure for hepatitis when you come to allocate the cash within your health service.
15% of Chinese children is a helluva a lot of Hepatitis and that's only HepB. There are five identified Hep viruses named HAV, HBV, HCV, HDV and HEV. In evolutionary terms they are as different from each other as viruses can possibly be - some use DNA to deliver their message and others use RNA, for starters - but all have in common a tendency to settle in the liver and replicate there. Their replication, as with all viruses, involves infecting a cell, subverting the local nucleic acid replication machinery to make more virus, popping that cell to release dozen or hundreds of infective units to recursively repeat the process and propagate the virus. The viral propagation thus interferes with normal liver function which manifests initially as fatigue, nausea and other flu-like symptoms which get labelled as hepatitis when jaundice develops. The cirrhosis and liver cancer will develop in due course if you live long enough. Anita "BodyShop" Roddick, for example, died of a brain haemorrhage before HepC killed her. Roddick got her dose from a blood-transfusion but many of the other celebs who have a HCV infection in common, got it from shared needles - don't do your own tattoos, kids.
We all take our liver for granted until it goes wonk and then we begin to appreciate how many and how varied are its beneficial functions. I could have had a lot to say about HCV, because its investigation formed a key thread in the Comparative Immunology lab in which I worked for the first part of this century. But the Blob logs show that I have been unaccountably quiet on the matter. Will rectify this in the future because there are some ripping yarns to be told. But for today, take 5 minutes to reflect on the 180 million people across the World who suffer [sic!] from HCV infection. Of these half a million die each year, which puts it at almost the same level as the big killers malaria, tuberculosis and infectious diarrhoea. Nobody has a developed a vaccine against that cause of hepatitis at least partly because, like HIV, it is a RNA virus which mutates so fast that it is hard for any vaccine strategy to keep up. Lots of science done, more to do.
Friday, 14 June 2024
Change Islands
My Parapals Rory and Alastair, for all that they mad-busy, are great readers altogether. I've taken on board a few of their book-recs out of respect to their sense of what's worth spending time on. The latest rec to be eased out of the library has been Radical Help: How we can remake the relationships between us and revolutionise the welfare state (2018) by "social engineer" Hilary Cottam.
Cottam's thesis is that William "Charterhouse, Balliol" Beveridge's 1942 vision for a Welfare State is no long fit for purpose in a post-industrial society top heavy with extractive plutocrats and ranks of declining Olds. And always the ♇!⊗king market, as if competition was always obvs better than community and cooperation. Maybe Capitalism = Koyaanisqatsi = "a state of life that calls for another way of living": Caring for each other is not about efficiency or units of production. It is about human connection, our development, and at the end our comfort and dignity.
In the UK, there are 100,000 neighbours-from-hell families, each of which is costing The State about £250,000 every year. One case study of a (single parent four offspring one preg) family in Swindon clocked 74 different professionals from 20 different agencies (tutors, counsellors, police, housing, health visitors, the social) involved in the family's care and attention. Cottam's people shadowed (with a time sheet) the eldest boy's social-worker and found that 74% of his time was spend on Admin (the forms, the forms); 12% on the phone haggling with other agencies; leaving 14% of the working week for actual work with the chap. But that social-worker's case load was much longer than one troubled teenager. 5½ hours a week spread across a dozen kids barely gives a social worker time to take off his coat, and in-fill another questionnaire before driving off to the next meeting. FFS don't use neighbours-from-hell and the like, it lacks compassion and smacks of hubris - the overweening complacency that it could never happen to me coupled with victim-blaming.
Cottam sets out the stall for the UK welfare state as it now stands. The Irish equivalent is not substantively different. When novel "obvious to all thinking people" good things are suggested, The State puts the kibosh on them double-quick:
- See the same doctor? Too expensive
- Help another person? Too risky
- Provide solutions through a known community group? Against the rules of competition
Manage need vs develop capabilities
The middle section of the book looks at left-field "Experiments" or pilot-studies with which Cottam has been involved; professing, if not actually solve, to ease the burden of problems in 5 areas where The State is only rearranging the deck-chairs and not delivering a lot. Well 1 million people are employed to help make things better for their fellow citizens - 1 million adults not collecting the dole, so there is that. For ten years, Cottam's NGO Participle did the state some service and demonstrated how agile, focused orgs might deliver more QALYs for less money.
- Family. Their Life programme set in place mentors / listeners who had time to listen to the manifold problems of the dispossessed; develop a holistic view rather than silo-thinking; engender self-respect by respecting the troubled rather than joining the line of comfortable people who want to beat on them
- Youth. Their Loop programme swept up lost youth and found them work-placements in the community - a bit like the best examples of Irish Transition Year work experience. The pilot study was going gang-busters with obvious benefirs accruing to The Yoof, The Community, The Employers. But when they held an open day for government agencies, the scheme was immediately closed down . . . because teens were developing a relationship with an adults who was neither a family member, nor a teacher. In the eyes of The State, all adults are potentially if not probably predators on the young.
- Employment. The first thing in Backr was to call out the complete failure of Job Centres to place the unemployed in work. They then created a network of MeetUps where job-seekers could network, commiserate, and even crowdfund money to get small businesses over the threshold for creating a new position.
- Health. Another problem, another daft label. Wellogram applies similar holistic views to health and well-being. It's normal now to refer people with unlabelled malaise deeper into the maws of the NHS. Maybe it's better to take them out of that mill altogether and treat their loneliness, stress, and feeling crap with kindness and a cup of tea. The GP has no time to listen and for some people some of the time, tea and chat is at least as effective as [and FFS cheaper than!] anti-depressants, anti-biotics or anti-inflammatories. Health education is the unsexy, unfunded, unseen part of the health service: but it doesn't have to be like that..
- Aging. The End is Circle. This experiment facilitated Elders getting together and telling each other that they could so do more for themselves rather than relying on the State or it's agents. Call me the complacent patriarchy but I've found that fixing stuff, making stuff, myself is empowering. It also frees me from dependence on someone else's timetable, engagement and priorities. And it saves money. I know, I know it's a short step from victim-blaming but making people do for themselves can be done with kindness, with panache, with respect.
There you have it. Dozens of ideas, thrashed out round a conference table, and rolled out into the local community. Some of the schemes are still chuntering along years after the initial funding dried up. Related to this is Samuel Smiles [prev] and his vision for the world in Self-Help (1859). But what do I know? I've returned Radical Help to the library. You can read it next. It might outrage you enough to do something different.
Change Islands? A decade ago The Blob wrote a neat 900 word essay about fishing on the North shore of Newfoundland, parcelled it up, tied it with a green white & pink ribbon and launched it into the blogosphere. The next day I butterflied off to write about Sellafield / Windscale about which I was marginally better qualified to express an opinion. That was then, this is now, and flitting about long ago and far away won't butter no parsnips.
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