Does a bear . . .?

The flush toilet is a terrible thing because it disconnects us from our own ordures: flush! flush! all gone! . . . to a place where somebody else [probably an untouchable] will deal with it. I am surprised at the number of people, even blokes, even blokes of my age, who are almost unable to have a pee anywhere other than in a designated toilet. Then again there is this obsession with TP / tissue that a) has to be used to dab-it-off b) left behind. I mentioned a particularly espanish egregious example a couple of weeks ago of people contributing their wee-litter to our farm. It was a perennial problem walking the Camino, where any and every secluded spot just off the pilgrim highway, where you might think of having a discrete pee, would be dotted with evidence that you weren't the first person to have that idea eeeeeuw watch your feet. If you had to work, or walk to the spring, for each gallon of water, you wouldn't be shitting in it.

Park that thought and get on your bike? MeFi flagged the inauguration of a new ultra endurance race GBDuro2019 in the UK (from Land's End to John O'Groats, of course). It's with bicycles and the rules of engagement is that you have to carry all your kit, and all your food with you. You can nip onto the shops and tap your cred-card for a Mars bar or a Cornish pasty, but you can't have your partner drive ahead with the 4x4 and have a hot hip-bath and a gin&tonic ready when you breast the top of Carter Bar. Nor can you stop off in a ***** hotel; if you don't plan to do a 600km stage in one almighty session then you're expected to sack out until first light in a bivvy-bag. "Riders should ride in the spirit of self-reliance and equal opportunity." and "There are no entry fees and no prizes. There are no officiators, no marshals, no ride leaders, no rescue services. There is no support".  Call me judgemental but if, on the Camino, you send your rucksack ahead of you by van (and you can, there's no longer a gap in that market) then that's not in the spirit of self-reliance and equal opportunity.
When I walked up the coast of Portugal in 1989 (heck! that's nearly 30 years ago), I was entirely on my own and on my own resources. There were no direction arrows, no hostels, no cell-phones, no GPS. The only reason it was possible at all at all was because the navigation was delimited by the sea. If I drifted too far East I got wet feet. GBDuro2019, for all its self-reliance is very much a child of the Age of WiFi - everyone has a GPS transponder and the route map is similarly on the GPS cloud. So you have to phone-check yourself all the time lest the true-route bifurcates from the you-route. It's nifty and graphic: like the still [above] from the documentary on this year's trek.  Because it's on the cloud, your Beloved or your fan-base can check your progress 60/60/24/7. The organisers a shadowy body called The Racing Collective [Гоночный Коллектив ?] request and require participants to tweet time- and place-stamped photos of their progress. It's not like when Zatopek won his marathon in 1952.

If Lachlan Morton looks lonely or like he's left everyone behind, it's because he has:

2,000km in 111.75 hours! Blimey!? That's as inspiring as the Appalachian Trail trials of Scott Jurek; the Iditarod dogs in Alaska; The Tarahumara in Mexico; the Barkley Marathons in the Tennessee wilderness. But let's get back down with the dirty: if you are off road and on your own and need a crap; what then? Well, The Kollectiv gets really exercised about this because soiling the route is showing contempt to those who come after you . . . and for the pristine natural landscape through which the riders are privileged to cycle:

• Don't be a dick - Leave No Trace (bring a trowel), be nice
• Further: Nothing beats a well-earned shit in the woods - fact. And whilst the "turn over a rock" method has been used for donkeys years it is no longer fit for purpose given the volume of people now going 'into the wild'. Indeed, failure to properly manage human waste has led to the death of other bikepacking rides such as the Oregon Outback. 
• [Here's a link to that sad and shameful story of heedless behaviour by adults]
• Hint: making a proper hole without a trowel takes a LOT of effort! So if you're riding GB Divide, please carry a trowel (at 17g it won't slow you down)

I've said enough, back to the filum!

Sunday Misc 210719

Hilarious homage and cultural update to Millet's Les Glaneuses.

• Florence Foster Jenkins singing for laughs: more people used to laugh at her than with her.
• Mossy Bottom. Advice to people with a fantasy of moving to an Irish small-holding.
• Frightfully English? Follow Max Fosh to Henley or Metal detecting
• France? Jumping the Tour de France on a mountain bike.
• Handling sourdough. High hydration means gloopy and in need of working.
• Food: Did someone mention Jamie "Bust-again" Oliver?
• Drink: The irrepressible Steve Mould on coffee acoustics.
• Acoustics also vital for skating on thin ice.
• Larry Earles Vietnam chopper pilot
• Can you imagine what it was like to be given a lethal toy like that in your 20s? Like my Dad in 1940.
• Trans-Atlantic fibre optic -a comms history.
• Did someone mention Ocean? Cue Nina & Frederick
• A long way from the ocean - Altai throat singing - more Baatyr
• I went to Vanya in the mountains
• Unstoppable that's what Georgia Shakestaff says [1min] about GirlsUp
• Willpower says Tanushah Ramadass
• Community says Musonda Chikwanda
• Henry Marsh author [prev] and brain-surgeon being engaging with Jim Al-Khalili

Little Dribbling

Hey lads, I finished another book. Bill Bryson's The Road to Little Dribbling More Notes From a Small Island [reviewed] which might be called Vignettes of Britain Vol II because it records a ramble 20 years after he published Notes From A Small Island. I've cited Bryson numerous times frequently to say that his Lost Continent is his original and best book. The world moves on with frightening speed and we have to hold on or fall off. In 1995, when Notes was published, I didn't own a mobile phone, climate change wasn't a thing, the Green Party was non-existent, China's economy was smaller than Brazil's. Many of the changes  between 1995 and 2015 to which Bryson reacts are for the worse.  A lot of butchers, bookshops, ironmongers in villages have been driven out of business by big box stores on the periphery of cities. Public services: transport, libraries, amenities, hospitals, schools have declined in quality in a relentless unwillingness to take taxes and pay for them. That's because he's a bit of a curmudgeon harrrumphing about the good old days of Britain in the 1970s when he first set foot in Europe on a gap year that became a life-time. I was there, though, and there was much not to love about England 1973 and I left for Dublin and a better life that October. But I will agree that 20 years of continued worship of the growth economy and a callous indifference to the dispossessed have not made Britain or Ireland better places to live for the majority of the population. Smart-phone eye-candy, frozen pineapple pizza, and dozens of pairs of uncomfortable shoes are irrelevant to well-being however you measure that.

The good thing about Bryson's books is that they are well-written and genuinely funny in parts, but they are also insightful, wide-ranging and fact-checked. If people read his books (and lots do) then they are better informed and tilted towards the good side of a well-run caring society. The down-side is that some really frightening changes in the state of the world are dug up, exposed to light, scare the bejaysus out of the reader; but then the narrative zooms off to the next chapter with an acerbic comment and we're back to hilarious take-downs random pompous or inefficient people in tourism or service.

• Sellafield has discharged more unaccounted nuclear waste than all the rest of the EU and contains the two most glowy buildings in Europe. 
• In 1950 Grimbsy landed 100,000 tonnes of cod. In 2015, 300 tonnes. That's a consequence of rapacious, unregulated destruction of underwater habitat in pursuit of fish-fingers. If only every fish caught had been used to feed people. In fact, thousands of tonnes of 'by-catch' just fed gannets and bacteria.

I used to read a lot of travel books; especially those that were funny, stoic and self-deprecating. But I'm not such a fan anymore. If you fillet out and discard the log-book entries of where the author went and how difficult it was to buy tickets, then you're left with not very much: met this bloke walking his dog who said . . .
But, if you like that sort of thing you could, with advantage, check out of the library:

• Peter Fleming (brother of Ian "Bond" Fleming): Brazilian Adventure (1933)  or One's Company (1934)
• Eric Newby: A Short Walk in the Hindi Kush (1958) or The Last Grain Race (1956)
• Ivan Sanderson: Animal Treasure (1937)
• Patrick Leigh Fermor: A Time of Gifts (1977) or Between the Woods and the Water (1986)

Rules for US places

It seems that Irish placenames are a bit of a free-for-all. I found two townlands, an hour's walk apart, both called Knockroe [The Red Hill]. Across the country, a rattly ould mix of names derived from Irish by translation [Dublin = the Black Pool] and by transliteration [any town / village / settlement called Ballyxxxxx]; from the local Anglo landlord [Parsonstown - not only what we now call Birr; Edgeworthstown which is fighting off the alternative name Mostrim; Newtownbarry losing ground to Bunclody].  This can result in some unintentionally funny / unfortunate coinages. A townland just West of Kilkenny City called Sceach na Míol = Hawthorn Crataegus monogyna of the jumping louse Cacopsylla crataegi becomes Lousybush in English to the mortification of the girls who live on the Dunningstown Road. Crab lice Pthirus pubis are very distantly related to Psyllidae: last common ancestor 400mya, so you gals can tell any ignorant slaggers, who bring this up, to piss off.

There is a certain irony in The Land of the Free having a much less free-for-all attitude to naming all the creeks, aroyos, peaks, mesas, runs, buttes and passes of their internal geography. Indeed they fund a Board on Geographic Names as a federal body operating under the United States Secretary of the Interior; they collaborate  with the US Geological Survey to run GNIS the Geographic Names Information System.
Q. Hey there's a system? run by the Feds? there must be some serious documentation?
A. True, dat: 85 pages of rules, policies, conventions, lists and appendices.

They are absolutely proscriptive about two pejorative words in place names Jap and the N-word. When civil rights got traction in the 1960s, fig-leaf changes were made: Negrohead, TX; Little Negro Creek, IL. And all the Japs got the -anese suffix. But places like Old Paddy Creek, MO; Kraut Canyon, NM; Wop Draw, WY and Dago Joe Spring, NV are not (yet) verboten. You may bet that the next unacceptable toponym will be anything involving squaw. You can search for your own name or naughty words in the database of 2 million named geographical features.

As well as avoiding offence, BGN wants names to be functional, so that they can be written on a map at a sensible font-size and not look bigger than the State Capital. US Postal Service limits Post Office names to 28 characters. So the petitioners' Rear Admiral Richard E. Bennis Reach, NC was accepted as Bennis Reach. Sometimes BGN just roll over as with East Fork North Fork North Fork American River, CA. I bet the BGN are aching to have a bunch of locals petition to rename that watercourse after a dead American hero . . . preferably a Native North American.

And for reasons now lost in the mists of time, the BGN hates possessive apostrophes. It is Pikes Peak therefore not Pike's. Likewise Butlers Toothpick and DEvils Racepath. Since 1890 only five exceptions have been agreed Martha's Vineyard, MA; Ike's Point, NJ; John E's Pond, RI; Carlos Elmer's Joshua Tree, AZ; Clark's Mountain, OR. Other accents and diacrital marks are accepted, indeed willingly embraced, although not essential to searching on their server: too many monoglot anglophone users to get pedantic about fadas.

Dogged does it.

As I push on towards retirement I am decluttering in a piecemeal kind of fashion. Off-loading stuff that I cannot imagine anyone having a use for.  My track record is not good for imagining uses for data. I was only annoyed when Craig Venter published a clatter of ESTs from a human brain: because ESTs are partial and of crappy quality and all I wanted were full length human genes which had been accurately sequenced. Wronnnng! ESTs are dead easy to generate and, because of their monstrous regiments, can be used to answer all kinds of interesting questions including one of my own [PMID: 12885301]. I can do methodical but I'm better at butterfly. The field I chose to work in 30 years ago doesn't give credit for drudges - folks who can plod through hundreds of samples and maintain the same standards of accuracy and reproducibility from start to finish. In bioinformatics, you get credit for scaling up an analysis by writing software that can do the heavy lifting, scouring and sorting through scads of data.

There is another class of scientists which I have characterised as A Good Pair of Hands. Like my student Grace who was the only one in the Microbiology class who could do a smart, reliable diagnosis with Gram stain. Turned out that she had spent the previous summer in an equine pathology lab doing dozens and dozens of Gram stains. I love doing Gram stains, she said, as she ploughed through a stack of them. As with so much in life practice makes perfect, but I knew that her managers in the equine lab developed an absolute trust on her reliability, accuracy and efficiency.

My brother tells a story about quality control QC technicians in a Volvo factory. The quality of the assemblies was so good that the QC checkers were falling asleep, day-dreaming and thinking about the weekend's soccer. Th QC manager decided to introduce a bunch of deliberate errors in the pipe-line: they came often enough and random enough to keep the QC techs on their toes and able to catch, not only the known errors, but also the unknown / real errors on the system.  I was reminded of this because of a recent molecular evolution report out of Tucson, AZ.

Michael Worobey, the PI, heard about an archive of 50+ year old paraffin-embedded tissue samples stored in cardboard boxes in the University of Kinshasa in the DRC / Democratic Republic of Congo [previously Zaire; prevprev Belgian Congo). Let us give thanks to inertia and a tolerance of skuzz and clutter that these slides hadn't long ago been tidied away to whatever serves for landfill in central Africa. Like all the unique irreplaceable photographs of olde time Tyneside that my pal Roy was unable to save from discard and destruction. Worobey has a track record in medical molecular archaeology, extracting DNA from old biopsies with painstaking care, so that the threadlike fragile genetic signal can be filtered out of the noise of time-degraded and potentially contaminated biological material. The samples were probably preserved by histologists who wanted to see what they looked like down a microscope. Nobody then knew that the DNA was useful / informative let alone how best to preserve that aspect of the tissue.  But there was a helluva lot of samples: N = 1652 to be precise, and someone had to process them all. That task fell largely to Worobey's Good Pair of Hands a fellow called Thomas D Watts. They were hoping for some ancient HIV on the assumption that these central African samples would predate the HIV/AIDS epidemic that started scything through young gay men in New York and California in the early 1980s.

Well they ran through all the boxes and boxes of material and came up with one (1) positive for HIV - a 38 y.o. male who presented to the hospital in 1966, where a peanut-sized chunk of a lymph node was taken for further study. Despite the lottery of history [116/123 of the plays of Sophocles have been lost] and because they have really good techniques for assembling fragments of DNA gathered in adverse circumstances, Team Tucson were able to obtain a more-or-less complete HIV genome sequence from this sample and compare it to all the subsequently evolved HIVs. There are, as yet, no known older HIV sequences which are mostly complete; DRC66 is the oldest. Evidence, from phylogenetic trees and molecular clocks, is pointing to the start of the 20thC for The Event that brought HIV-I across the species divide from chimpanzees Pan troglodytes to us Homo sapiens. Watch this space as researchers get dustier colonial times boxes from peculiar places to find older HIV positive sequences. These will almost certainly be confirmatory, it would be surprising if something startling emerges from similar studies. But the Tucson study is valuable as an anchor-point for the inferences of phylogenetic trees generated by computer. If this is HIV-I, there is an HIV-2, right? Indeed so, HIV-2 crossed in humans from the sooty mangabey Cercocebus atys. That strain is much less virulent and infective, so is rarely seen outside of West Africa.

Remember Ebola? That had us all up in a flap 2013-2016 and was almost a case of too little, too late? The mainstream media are tired of Ebola and don't want to be seen to cry wolf. Nevertheless, Ebola is back and has been flagged with global emergency status by the World Health Organisation. And the epicentre of the latest holocaust? DRC!

Intentional living

BBC has a polemical documentary about reducing food waste. The compelling statistic is that a third of greenhouse gas emissions are due to food rotting away because it cannot be sold or won't be eaten. And a quarter of food-grade food never gets eaten.
Verspilling is Verrukkelijk = Waste is Delicious is a food recycling scheme invented by Jumbo, a Dutch supermarket chain. TheyToo good to go
Here's a Tasmanian family, home-educating who have refused a plastic life and go shopping with bottles and cotton and paper bags which get used again and again. Actually, they have plastic snap-lid containers which get filled at the butcher and fishmonger [as R], so their beef is zero waste rather than zero plastic and they have been trundling along in that mode for 3 years. Home education must make it easier to get compliance with /from the three daughters-of-the-house a) because their home ed pals are quite likely to be on a similar trajectory b) because they aren't subjected to an invivious amount of peer pressure [to get the right shoes, right phone, right play-list] at school. But some of the trotted stats boggle the mind "the average Australian family generates enough waste to fill a 3 bedroom house every year". I've just spent 2 nights in refuse-collection land with Pat the Salt my aged father-in-law. We put out a brimful 240 lt wheelie-bin on Wednesday morning that's 240lt [¼ cu.m.] * 52 weeks = 12 cu.m.  That's only the smallest bedroom full, not an entire house, cobbers.

Here's another supply and demand problem if you're British. BBC Newsnight reports that hoarding and stockpiling will be at nothing, unless it's garden furniture and safe to be left out in the rain. There just isn't the warehousing capacity to store the food and medicines needed to buffer a crash-out Brexit. But no competent prepper would put any trust in The Man to ensure enough bread and booze in the shops; nope! they will have bought a garden shed [as L 8ft x 8ft, = 6 sq.m. volume ~= 15 cu.m. a snip at £900 delivered] to store the beans and ammo. That's about 20,000 500ml tins of lager one-a-day for 50 years. But after the apoclaypse it won't just be beer and skittles; we'll all need beans as well. A tin of beans being slightly shorter but slightly stouter than a tin of lager, the same shed can store about the same number of bean-tins.

Really new antibiotics

I R old, which is an extraordinary consequence of having been born in 1954 when infectious diseases were being run out of town by a combination of vaccination and antibiotics. My father contracted pneumonia in 1925 and it was touch and go for several days as his 8 y.o. immune system played chess with death; but he was a fighter like Bergman's knight and eventually he pulled through, worn out but alive. 70 years later, 2 y.o. Dau.I also had a brush with pneumonia and spent 2 nights in the Children's Hospital but antibiotics made the episode almost a walk in the park rather than a walk into  the dark . We have squandered the healing elixirs on dog's ear-aches and as growth promoters for battery chickens. A few years ago, I went grimly poetic about an apocalyptic return to a world without antibiotics. In that grim new reality, children will die from a thorn-prick, or diphtheria or scarlatina as they did 100 years ago. In 1900 infant all-cause mortality fluttered around 16%; in 2000 it was less than 1%.

MRSA isn't usually a problem for kids, but it will exit your Auntie Flo in a box when she goes into hospital for a hip-replacement. I've had a lot to say about MRSA [bloboprevs] before. Not least because we could have been contenders in the search for novel therapeutics against this strain of Staphylococcus aureus. One of the anti-microbial peptides that we discovered lurking in the chicken genome, turned out to be quite good at killing MRSA and a little bit better at that task when we tricked about with the peptide sequence. If only MRSA was the only species that was resistant to almost all the antibiotics, but hospitals particularly are also held hostage by Carbapenem-resistant Enterobacteriaceae or CRE. As if a blizzard of acronyms - all including R-for-Resistant - is insufficiently confusing /worrying, the meta-acronyms ESKAPE identifies the causes of most concern - S for Staphylococcus aureus etc.

In the bizarre market-driven world of Big Pharma, there is little incentive to develop novel antibiotics. The big players see more $$$s for shareholders by focussing on chronic disease which will keep on demanding therapeutic supply for decades. To keep people ticking along feeling crap is better for business than infectious diseases where the patient is either cured in a week or dies - neither outcome being a cash cow that keeps on giving.  Any work being done with antibiotics by Big Pharma is most likely to be tinkering about with chemical structure of known bacteria-killers to produce a Me Too variant that can be patented because it is technically different but is so similar to existing antibiotics that resistance can be expected even sooner than average. The microbe collective has the number of whole classes of antibiotics. Another issue is that newer antibiotics are edging over the line in the balance between safe and effective. They kill the invasive bacteria, yes; but they also do damage to human cells and systems. Even to the extent that we cured the infection but the patient died. What we need, what sick kids need, what the medical front-liners need is some wholly new, now for something completely different, antibiotics that will win a few years of effectiveness (and safety!) rather than a few months.

Thankfully some academic scientists hanker after being the next Alexander Fleming (and thereby having a shot at a Nobel Prize in 10 or 15 years time. A number of creative scientists have had a punt in the direction:

• Kim Lewis and Slava Epstein invented a gizmo for isolating single killer-bacteria from a soup of soil and isolated a potent bacteriocide from a totally new species they called Eleftheria terrae.
• Paul Dyson and Dusica Vujaklij's key insight was to read the medieval medical literature to isolate an ESKAPE killing Streptomyces from an Irish churchyard

Now Brice Felden's lab at U. Rennes in Northern France have made a startling, sparkling discovery by modifying part of a known toxin produced naturally by Staphylococcus aureus. Their key insight was to separate the toxic-to-humans aspects of the Staph molecule from the toxic-to-microbes parts. Evolution so often produces a kludge - something that works even of it has some peculiar side-effects. "Works" means enhances the survival or reproductive fecundity of its owner. A large part of modern molecular medicine is trying to dice and fillet and modify molecules so that they work better in the system being investigated. Team Rennes looked at the sequence of the natural toxin and started to strip out chunks and test them for their anti-microbial properties. One amino acid sequence FFWRRVK showed promise when they made artificial copies of the linear sequence and linked the ends to make a circular molecule [Pep18 below]:

So far, so natural, but they did some combinatorial experiments to see if they could make an even better microbe killer by swapping out the natural amino acids for wholly artificial molecules. Pep19 has acquired two aza-β3-1-naphthylalanyls to replace the 1st F and the 3rd W amino acids. Naphthyl as in naphthylene = mothballs. The Team in Rennes have some really promising results showing that some of the 20 molecular variants they generated can be granted the three-fold palm of success:
1) kills a wide range of bacteria
2) does little damage to mammalian cells
3) seems to stave off the development of bacterial resistance to attack
They will be looking for venture capital to take their hope-for-the-future up the regulatory chain towards a marketable and life-saving addition to the medical war-chest.