Hello LO

L is for list

• Liszt? Now there's a composer I know rather poorly. I've heard some of these before but couldn't have put a name to any of them:
• La Campanella
• Un Sospiro
• Valentina Lisitsa plays Liszt 2nd Hungarian Rhapsody
• Totentanz
• Luka: Suzanne Vega's surprise hit
• Longyearbyen, Svalbard, seeds, bears and snow.
• Legrand, Michel, dead in Paris
• Windmills of your mind
• Les Parapluies De Cherbourg
• Llewellyn, Sarah: multitasking well peculiar.
• Lysistrata: Aristophanes' play about sexual politics explained
• Leatherback Sea Turtles Dermochelys coriacea in Irish waters <10Mb, 32 pp.>
• Lloyd, AL & MacColl, Ewan
• South Australia
• Shoals of Herring or by Luke Kelly
• Loofah pathology (use bleach)
• Loxodonta africana - african elephant
• It's a piano piece too
• Lend-Lease US to USSR
• Sing it
• Lurry it in: Breakfast for 1500 US Navy champions
• Leaves on the line - Steve Mould [prev] experiments
• L for Lasso a new American hero
• Lotus Puzzle: a new vicarious entertainment for sofa sitters - watch a man thinking.
• A bad day for the Lannisters

Driving Miss Ursula

I occasionally scan 3quarksdaily to see whaaaaat's happenin'? on the liberal arts front. A tuthree days ago I was pointed to a delightful essay in Granta in which Alison Smith gives a very personal tribute to Ursula le Guin. In 1988, when Alison was 18 and Ursula about 40 years older, the famous writer came to visit Rochester NY and the young student was assigned to be her gopher-chauffeur for the week. Alison had been a huge fan of Ursula's books since she was a bookish sub-teen but didn't get gushy and completed her minder's assignment with discretion, honesty and empathy. My reading is that the author found her company far more congenial than that of the English Faculty, who covered their awe of the famous write with a layer of bluff blokey bravado that must have been tedious if not oppressive. By the end of the week young Alison had been transformed by the respect and kindness of the older woman into someone with ambition, confidence and a, probably misplaced, fascination with French culture. She was also determined to be a writer, rather than having pretensions to being an author. To this end she started writing, more and with more regularity [ahem - like myself], until now 30 years later she is scrabbling some sort of a living from her craft. You should read the memoir. If you have a bookish, possibly gay, teenager / twenty-something about your household then you should be sure to make a copy for them. Ursula le Guin died this time last year - I've written my own tributes.

About 15 years ago, The Beloved TB came out . . . and embraced the practice of the Vietnamese peacenik and Dharma teacher, Thích Nhất Hạnh. After being exiled from his native land during the Vietnam War, TNH started a community in the Dordogne Valley in SW France called Village des Pruniers / Plum Village. Round about the time that I went on my transformative pilgrimage to and from Santiago de Compostella, TB went to Plum Village for a week of meditation and silence and underwent her own transformation.
We subsequently fixed up a telephone booth in the yard at home to facilitate our emergency clothing changes before flying off to rescue sheep caught in wire fences. In 2006, we took Dau.I and Dau.II to Plum Village for the Summer Retreat because it was billed as For Workers in the Neurosciences. I've written about how a succession of contingent accidents found me addressing 1,000 participants about Mindfulness in Medicine. I was famous for five-and-a-half minutes [me and Onnie were so taken with the theatre that we ran over by 30 seconds].

In 2011, Plum Village announced that, as their retreats were getting flooded by Irish citizens in need of mindfulness, Mohammad TNH would proceed to the mountain four green fields of Ireland . . . and could somebody local make that happen? That somebody materialised as a small committee of dedicated TNH fans including The Beloved. It was like having to organise part of the World tour of a middle ranking rock band [with fewer drums and guitars, but more bells and saffron. . . and no drugs or alcohol]; because Hissonour announced that his party would include at least 50 monastics from Plum Village. The Itinerary settled down to a) Filling the Dublin Convention Centre with 2,000 bodies for an evening talk; b) Filling the Killarney Convention Centre for a three-day retreat for 800 people; c) Addressing the Norn Iron Assembly at Stormont. A succession of contingent accidents found me as the designated driver of the Popemobile a rented 7-seater people carrier. With my grey hair, dismal-Eeyore demeanour and dressed in my interview-wedding-funeral suit with a sober tie, I looked the part. A peaked cap would have degenerated the costume into parody, so I skipped that.

Very respectful I was too:  not speaking unless addressed, not restlessly searching for soccer commentary on the radio, doing my best to go easy on the gear-changes. There was one dicey moment on the way up to Stormont [R] when I missed a turn in suburban Belfast and did a quick-thinking U-turn neeeeooooww across two lanes of oncoming traffic. The monk sitting in the passenger seat turned a whiter shade of pale but the VIPs in the back seats were in a state of satori - they didn't yelp! anyway. The following day we headed back to Dublin. TNH elected to sit in the front seat to see a bit of the countryside; his team of attendants sat in the back singing Vietnamese pop songs and generally larking about - because the Stormont gig had gone rather well and we were all relaxing. TNH was quietly amused by a sign on the Gormanston toll-booth:

 Arrive Alive 

and when we finally pulled into the place they were staying in Dublin that evening, he put his hand on my arm and said "Arrive Alive" with a little nod of appreciation. Maybe he'd been more alert than I thought when I did the two-wheeled U-ie the day before.

Chunder rice

Being hospitable folk with a few drops of Irish blood, we always cook for the unexpected guest. D'ye remember the old instructions for making a pot of tea: "a spoon of tea for every person round the table and one for the pot" . . . that resulted in tea the colour of tomato soup and able to strip the skin off your palate? . . . not to mention strip the enamel off a tin plate. There is always something left-over in a small pot in the fridge: half a cup of rice; a portion of caldo verde for lunch tomorrow; the last two boiled potatoes; a corner of lasagna. As we gave up on microwave ovens some years ago, these bits and pieces require some ingenuity to make palatable - and safe.

At The Institute, we're in the middle of Yr3 Food & Fermentation Microbiology, this week we're hoping to isolate Gram-positive spore-formers. That would be Clostridium spp. and Bacillus spp. F&F is an introduction to microbes that are either a) essential for the making of some foods - Lactic Acid Bacteria LABs mainly or b) bacteria associated with food spoilage. Clostridium [botulinum] - [tetani] - [difficile] and Bacillus [anthracis] are in a third category c) microbes that will kill ya or make you give at both ends.  Most years, I remember to tell the students about the problems with eating re-heated rice - it's the Bacillus cereus silly. That's relevant in this context because these bacteria, when confronted with adverse circumstances - drying out; boiling water; 70% alcohol; caustic soda - can curl up into a ball and wait it out.  This "spore" is remarkably robust to external insult and can be remarkably long-lived. One of the concerns with the melting of Siberian permafrost is that it will wake up Bacillus anthracis spores which have been in limbo for hundreds of years and release a pestilence of anthrax through any caribou and people who get downwind.

But, I add, nonchalant-like I've been eating re-heated rice on a weekly basis for 4 or 5 decades and I've never had to talk to the porcelain telephone.  Nor has anyone in my family. B. cereus is a natural inhabitant in soil and on vegetation and appears to have a particular preference for rice. You boil it up and that kills almost all the bacteria but some of the B. cereus start the sporulation process and hunker down to wait. A hour later, the temperature is waaay down and the bugs start to wake up again. If you slam them in the fridge at 4^oC that will put a stop to their gallop by slowing their cell division but it won't kill them. Every time they are left at room temperature for 30 minutes they double their numbers. Leave them over-night on the counter and they will have increased 2^20 = 1 million-fold.

Here's an interesting but tragic story of an adverse event: A Student Ate 5 Day Old Pasta For Lunch. This Is How His Liver Shut Down. Title says it all: poor fellow died of acute liver failure from the toxins produced by B. cereus but made his prognosis much worse by topping off his fizzy pasta with a generous slug of aspirin [it's the Reye's Syndrome silly]. via MeFi where lots of on-topic discussion and commentary.

You know the Aussie for vomit = Chunder?  supposedly shortened from Watch under! A list of synonyms seems like a bowlful of funny perhaps because they sound the part - barf, hurl, chuck, boke, ralph, hork, puke, spew, heave, yark, york . . . and the phrases: whistle beef; technicolour yawn; russian salad [L]; woof cookies; bark at the ants.

Helping yourself

Earlier this month I was a bit jaundiced / skeptical about finding a cure for alkaptonuria. It may work out for Nick Sireau and his boys but nitisinone is not a cure: it just transfers the molecular rubbish to another place. You don't get the dark-skin, joint-pain and eye-damage but you get "elevated tyrosine levels, thrombocytopenia, leukopenia, conjunctivitis, corneal opacity, keratitis, photophobia, eye pain, blepharitis, cataracts, granulocytopenia, epistaxis, pruritus, exfoliative dermatitis, dry skin, maculopapular rash, alopecia, bloated abdomen, dark urine, abdominal pain, feeling of tiredness or weakness, headache, light-colored stools, loss of appetite, weight loss, vomiting, and yellow-colored eyes or skin . . . instead. I have been critical of fantastically expensive, marginally effective drugs getting pushed by politics, instead of being refused licence by accountants. Parent's lonely fight to save compromised child is A Story which a hungry free-lancer can write up for the Grauniad, the NYT, or the Sligo Champion. Search keywords: quest, desperate, fight, tireless, crusade, tragic, diagnosis, genetics.

A week ago, a variation on the theme popped up on MeFi [comments informed and wide-ranging] and I followed through to Wired for one of my 3 free reads there this month. The hook here is that, although there is a cute toddler, it is the girl's mother who is trying to save herself from a late-onset, rapidly degenerative brain disease called fatal familial insomnia FFI. Sonia Vallabh and Eric Minikel [looking right sciency L - NPR source], who knew bugger-all science before Sonia's fateful diagnosis, went back to college and eventually got to be lead authors on a massive paper in Science Translational Medicine which compared the genome sequences of thousands of people with prion diseases and thousands of unaffected controls. They also set up a company (Sonia was a lawyer) Prion Alliance as a vehicle for gathering slabs of money for The Cause.

Prions have featured semi-incognito on The Blob as Kuru; they are also involved in Mad Cow Disease [aka bovine spongiform encephalopathy BSE], scrapie is sheep and the human equivalent variant Creuzfeldt-Jacob Disease CJD. It is news to me but FFI is another prion disease triggered by a different mutation in the PrP [Prion Protein] gene.

The PrP gene is found in all mammals and may have an essential function in copper transport, and/or something to do with synapse health between neurons and/or some association with circadian rhythms and the sleep/wake cycle. Bad things happen when the protein derived from the PrP gene flips to a 3-D structure that a) cannot flip back to normal structure and b) cannot be broken down by clean-up enzymes or undone. It then accumulates in lumps, especially in the brain, causing a cascade of unpleasant neurological events to occur: incontinence, blindness, loss of speech, loss of swallow, twitching, dizziness ataxia, insomnia. Death follows about a year after first symptoms.

It is believed that the flip to the indigestible form of the protein can be induced by contact with another copy the misfolded protein . . . acquired through the diet by eating meat from a Mad Cow or through blood transfusion from someone who has eaten some of that meat and is now in limbo waiting for symptoms to appear. The Irish blood transfusion service IBTS refuses donations from anyone who lived in the UK during the 80s when variant CJD and BSE were being revealed in that country. BSE was spread through the sketchy agri-practice of feeding cattle a protein-rich feed . . . made from ground up cow-parts. The same intensive cattle-rearing practice was going on in other European countries at the same time but the French authorities, for example, didn't look very hard for BSE and so found no cases. French blood is thus acceptable to the IBTS but not mine or that of any of the thousands of Irish people who lived in England in the 80s because there was no work in Ireland. Shamefully, only 4% of adults in Ireland are blood donors and I think the IBTS really needs to do a risk assessment on excluding me and The Boy and The Beloved and three of her siblings.

One of the interesting fall-outs of the scientific community acquire two smart committed grown ups to do research in FFI, is that Sonia and Eric came with a different tool-kit, different expectations and different ways of thinking. They were a real asset in lab meetings because of this intellectual flexibility which provided alternative viewpoints; perhaps especially in response to "that's impossible".

More women in science

Where there's muck, there's brass

Have I told you about fatbergs? I have, begodde! We were down for lunch on the Wexford Coast on Sunday and very nice it was too. It was sharp and sunny outside with the Kerragh Islands on the horizon black beyond a greeny sea. I was glad we could sit beside a roaring log-fire rather than garnering virtue [and yet more plastic buoys, rope and fish-boxes that I really have a use for] with a walk along the beach. As householders myne hoste and I were comparing notes about storm damage and house-keeping. It seems that a few months ago, their foul-water pipe backed-up from a sclerotic clot of congealed fat. They hadn't been as obsessively careful as us about washing greasy plates and pans in the kitchen sink and the residue had come back to bite them. For a variety of reasons, he elected to clear the pipe chemically rather than mechanically and dumped a load of hot sodium hydroxide / caustic soda / lye / NaOH down the kitchen sink and left the room. It was okay in this sense - that the water started to flow again. But he hasn't done a colonoscopy yet to estimate when he should buy the next packet of NaOH. Basically what's happening down there is that the Na⁺ and the fat are making soap which, as you know is water soluble. If you could get a really good marketing team in place, you could do this on an industrial scale with matter from fta-clogged pipes and sell the soap under a brand-name like Flush!. Well it's a better name than Enema - the soap that cleans the darkest places.

The after-lunch chat shifted slightly from cleaning out fatbergs to monetizing them - but not as soap but rather as bio-diesel. Argent Energy from the English Midlands is actively scavenging fat-bergs, and heating them in a huge vat - remember that these slug-like tangles can weigh in at 10 tonnes or more. The wet-wipes, sanitary towels, hair, dental-floss and nappies (who would throw a diaper down the t'ilet? What were they thinking?) all sink to the bottom or float to the top and the now liquid grease can be run out of a spigot at the base of the vat. Like pressing olives, you could have first run extra virgin diesel and them squeeeeze the mass until it yields the last drop of discoloured goop.  When the hot liquid cools, I'm guessing that like chicken stock, the fat floats to the top and the water-soluble proteinaceous soup sinks. I was making soupe aux choux over the weekend, for example, and the liquid cooked out from the belly of pork cooled into a rich brown gelatinous stock covered by a layer of pure pork fat.

The Argent plant in Ellesmere Port near Liverpool can recover 25%-40% by weight of oil from fatberg and has a production capacity of nearly 100,000 tonnes of the good stuff each year. Previous to their enterprise, fatbergs were a hazardous, noxious waste product that was burned or land-filled. Now it's getting a second lease of life in a repurposed form before it goes up to make carbon footprint in the sky.  Argent has a regular order of 30 tonnes a week from one [large] sewage treatment plant in Birmingham. There are 9,000 such places in Britain.  I hope it works out for all parties.

Alkaptonuria

When I was learning genetics in the 1970s, it wasn't quite possible that an ambitious graduate would know ALL there was to know in the field; but it was surely a lot simpler and less extensive back then. The half dozen standard text-books all re-hashed the same war stories to illustrate the most exciting or the most fundamental aspects of genetics. One well-worn story was about resistance to malaria effected by being a carrier for the haemoglobin variant that causes sickle-cell anaemia. That revelation was largely the work of a single medical geneticist called Tony Allison. Another of the paragons was Archibald Garrod [R as a suited Edwardian walrus] an English physician who pioneered the field of inborn errors of metabolism. We would call them genetic diseases now. The deal is that:

1. people are clearly not well; 
2. their adverse symptoms make a distinct syndrome which can be recognised in other patients
3. some of those other patients are relatives of the first case. The disease runs in families, to the extent that, in some cases, you could find distant cousins by their shared medical peculiarities.

What is remarkable about Garrod is that he worked out the genetics of Alkaptonuria and published it in 1902. This was barely a year after Carl Correns, Hugo de Vries, and Erich von Tschermak-Seysenegg rediscovered Mendel's laws of inheritance. Effectively, when Garrod started his investigations, there was no useful knowledge of Genetics, so he was working blind. Alkaptonuria is rare, distinctive and peculiar. The most obvious early symptom is that patient's pee turns black in the piss-pot which must be disconcerting  when first noticed. As these symptoms kick in before weaning, it is the parents who are distressed. Garrod didn't know what the biochemical cause was, but he mapped out pedigrees and proved that it was inherited as an autosomal recessive. That phrase means that the disease is a) as common in boys as girls b) it requires both parents to carry the defective gene. Years later, it was established that the black stuff was homogentisic acid; a metabolic breakdown product of the amino acids tyrosine and phenylalanine. It gets peed out because a key enzyme in its metabolic pathway, homogentisic acid 1,2-dioxygenase, is missing or defective. There is no cure and the disease is progressive: the homogentisic acid can't all be forced through the kidney tubules, so the toxin accumulates in the joints, under the skin,around the heart valves and in the eyes. It's a bit like gout, therefore, where uric acid crystals accumulate in joints. Longevity is not affected but quality of life definitely goes downhill and modern treatments involve hip and knee replacements when these joints become too painful to use. Phenylketonuria PKU is another inborn errors of metabolism from the same aromatic amino acid degradation pathway. That condition is identified within hours of birth with a heel-prick test to yield a few spots of blood on fiche of blotting paper.

Being of historical interest and colorful is not sufficient to trigger a Blob on alkaptonuria but a four page article in last week's Nature adds sufficient weight. A father’s fight to help his sons - and fix clinical trials - Nick Sireau’s quest to give his sons weedkiller could help thousands struggling with rare genetic conditions. That about sums up the sensational aspects of the essay. The problem is that nobody should want to 'fix clinical trials' unless it is the share-holders and sales-force of the pharmaceutical company which is marketing the therapy. Mr Sireau's boys were born with alkaptonuria and he was determined to find a cure, preferably before the lads grew up and started to show the worst of the symptoms - typically in their 30s.

There is a cure, of sorts, but because alkaptonuria is so rare it is hard to get sufficient numbers to carry out a clinical trial of its efficacy. Nitisinone [structure L] also interferes with the correct function of the tyrosine degradation pathway but one enzyme upstream as shown in the metabolic pathway [above L]. Under this drug's regime there is no accumulation for homogentisic acid because there is no accumulation of its immediate precursor. This means that other tyrosine degradation products, from further up the chair, do accumulate. Although the diet can be restricted to minimise the intake of tyrosine and phenylalanine, and that helps also.  The pathway, as we now understand it, shows just how complicated things can be to keep things turning over and keep essential nutrients like tyrosine and phenylalanine in homeostatic balance - so that they are present in just right Goldiloxian amounts. And for most of us, most of the time, it all works nicely, but disable any one of the multiple steps and the whole elaborate pipeline is banjaxed.

Nitinisone costs about $50,000 or $60,000 per person per year and they've done the figures on using it to treat Type I Tyrosinaemia a disease caused by a defect in the same pathway as alkaptonuria and PKU. Mr Sireau believes that it will have positive effects for his chaps but there is no good evidence that it makes the adverse symptoms measurably better. The US Food and Drug Administration FDA won't allow the drug to be marketed without that sort of positive benefit data. Nobody should be allowed to pay so much for something that doesn't work. Especially, this should be stopped if somebody else is picking up the bill. It seems that Sireau's advocacy group has blagged the European authorities to accept a less standard of 'success'. If, under treatment, the concentration of homogentisic acid falls significantly then that will be enough - it will be what is called a surrogate marker.  We-the-tax-payer will then start paying for the drug regardless of whether the 'real' adverse symptoms like pain, joint flexibility, heart dysfunction, eye disease improve. If it don't work; don't pay for it. It's better to grimace and bear it without treatment than to grimace just as much and be out of pocket. I dunno, I'm not certain about the ethics or economics here: you read the Nature piece and decide where you want your share $50,000 allocated. Trolleys? More nurses? Pay-hike for nurses? Mental health? New children's hospital? OR "I'll keep my share of tax-dollars, thanks very much, less tax will mean I can build my much desired (and to be admired) gazebo in the back garden"

A final grimace and bear it irony. Archibald Garrod had three sons. They all joined the army in WWI and they were all killed: Thomas 10th May 1915; Alfred 20th Jan 1916; Basil  4th Feb 1919 (Spanish 'flu). No amount of money could save them.

I demand to have some booze

New Year's Day I was looking through our Christmas Hamper from Baskets Galore. As with the rest of Christmas fare, I scanned the sell-by dates and started on those goodies most nearly gorn-beyond.
 4 Luxury Mince Pies    with Brandy  (05 Jan 19) had to go down the hatch first. With the  Brandy   and all, I was careful not consume any of them if I was planning to drive.

But what is this? The declared ingredients:
Pastry (Butter (Milk), Flour (Wheat flour, Calcium, Iron, Niacin, Thiamin)), Sugar, Water)
Mince filling: (50%) (Apple, Sugar, Waxy Maize Starch, Water, Dextrose, Preservative [E202, E260], Mixed Spice (Coriander, Cinnamon, Ginger, Cloves), Caramel, (Glucose syrup), Dark Vine Fruit, Mixed Peel, Vegetable Suet (Non Hydrogenated Oils (Palm and Sunflower)
(Wheat flour, Calcium, Iron, Niacin, Thiamin))
contain a lot of sugar (Sugar, Sugar, Dextrose, Glucose Syrup) but not even a sniff of Brandy. E202 is potassium sorbate and E260 is acetic acid - neither being ethanol let alone brandy. Altrhough acetic acid [=vinegar] is a natural oxidation product of ethanol.

I demand to have some booze! [Withnail alert]
I've written, more in sorrow than in anger, to Baskets Galore and Ditty's Home Bakery, but after a full working week no answer is forthcoming.

I was on about the ToC of (unboozed) mince pies a little over a year ago