Bah. Humbug.

So, I was going to say:

Here we are in the season of Merry Christmas and Happy New Year and etc etc posts where everybody looks back and goes over all the cool stuff, and wishes everybody else all the best and etc and etc. Good cheer and suchlike all around.

pfff.

It's been a rotten past several months. Sure, things happened before that, stuff that at the time was full of joy and wonder and I could hardly wait to write a year-end post like the others.
Now here we are at the year's end, and I just want it to be over. Please go back to normal, everybody.

And then I thought, if you don't have anything nice to say, don't say anything.
Well, alright. I'll just stop blogging. Get off Facebook.
But what's the point in only sharing nice things? It would be great if there were only nice things. But there are other things too. Isn't life poorer for pretending there aren't? And, if you don't have anything sweet and light to post, and you step out of the social circle, don't you isolate yourself even more? Isn't keeping a hand in part of what's going to bring you back to a place where good things happen regularly?

Do have a good day tomorrow. And better ones after that.

GET OUT

Ces plantes n'ont pas encore été composté, si tu veux les chercher.

Snarkiness -Or-

100 words on Why I love this Manuscript

Unsupported suppositions

Incomprehensible hypotheses

To our mind

Over-interpreted p-values:

If it’s statistically significant, it must be important

105 words when 10 will do.

The related statistics do not mean much.

Throw it all into a sack without controlling whether it belongs there.

Long meandering sentences with conjunctions that make no sense and verbs so far from their subjects you have no idea what is connected to what : always interrupted with a colon and frequently also with parentheses for self-referring references.*

Oppositely

We have the biggest database we know about.

Erroneous conclusions.

* I can’t even write that kind of sentence when I’m trying!

X

Nijmegen 2

The 16th A-T Workshop will be held in Beijing next fall. I went to my first ATW, the 5th in the series, in 1993 as a graduate student. 22 years later they're still having them, they're still announcing progress, and they're still looking for a cure. Family-run funding organisations have come and gone. Parents and patients are continually hopeful and disappointed.. One said I gave you millions - where's my cure? Forever elusive.

A couple of treatment options are tentatively on the table, though neither is a cure. Both carry risks. Neither can be tested in a randomized study. People don't agree about going forward with either one. Nor do they agree it is better to be careful.

As often happens, people start leaving before the last session. Trains and planes to catch now or wait a whole day. I'm waiting a whole day, mostly on purpose. This way I have the afternoon to see the town. Not to mention I hate meetings where the last speaker talks to an empty room.

I also hate travelling to a place for a meeting, going straight to the hotel, getting to know the venue really well, and then flying straight out again. Last night's little excursion notwithstanding.

Nijmegen? Oh, I've been there. Really nifty hotel out in the Berg en Dal region.

After a quick lunch I get my camera and check out the 90 minute trail around the park and agricultural area near the hotel. There are several viewpoints marked, but you can't see much from them. The hills aren't very steep and the trees still have most of their leaves. Makes for a nice view of the trees, but they get in the way of any view over the plain.

Now for a bus into town. The oldest part is off-limits to cars, making several blocks of pedestrian-district filled with shops and restaurants and today a long series of outdoor stalls along the main road means the central road is elbow to elbow with people. Throngs. Most of the architecture has been updated, and as I mentioned the large majority of shops are international chains. I'd like to pick up some unique souvenir, something that to me will say Here, without being a chunk of airport schlock made in China. I come across a place selling teas and coffess, with a gorgeous but limited and extremely expensive selection of hand-made pottery. Beautiful stuff but it will be difficult to get home intact. Perhaps I'll stop back for a trinket if I don't see anything else.

Ah, here's Hema. Load up on munchies for home and dutch cookies to share at work. By the time I come out of Hema it's getting dark and the open-air stalls are beginning to pack up. Hey, guys, it's not even 5. Ever thought of outdoor lights?

It starts to rain so I duck into one of the brasseries on the main street for a glass of wine and a cup of spicy tomato soup. Lots of people stop in for an afternoon beer or even dinner.

When I go out again the rain has stopped, the stands are in the last stages of packing, and the streets are deserted. The larger stores are still open, but nobody much is in there but the employees tidying up.

Saturday evening (not even - it's just late afternoon still, according to most of us) and Nijmegen is dead. Maybe they've all gone home for a rest and a shower before coming out for a wild night. Maybe.

I just don't really see that, though.

Several blocks later I catch a bus back to the hotel.

5:48

After a scalding hot shower I spend a quiet evening with a book.

At the desk they told we there were trains to Schiphol at 8:42 and at 9:12 that should get me there in time for my flight. To catch the train there are busses at 8:19 and 8:49.

Earlier is better, you know, just in case.

As usual I'm quick to get ready in the morning. I hang around the lobby interminably, then go out into the drizzle to the bus stop. The two blocks don't take nearly as long as they should, so I have plenty of time to hang out at the bus shelter in the dark, pacing against the cold. The rain is weak but makes a lot of nouse in the trees. Leaves come down as drops hit them just right. A day or two of this and they might be naked. The sky lightens gradually, and by the time the bus arrives it might be daytime. Hard to tell. Certainly it is by the time we pull up at the train station.

I have just four minutes to buy a ticket, find my train and get on it. For natives this might be child's play, but my dutch is rudementary. Good thing I have enough margin to take the later train.

Aha. Train to Amsterdam at 8:42, just like the desk clerk said; there's only one leaving at that time, and I find it & hop on just before it starts rolling.

Looking at the display of stops, though, this train does not seem to stop at Schiphol. Um. I suppose trains back to Schiphol from Amsterdam Central must be frequent and quick. Though I know that is a 20 minute trip - good thing I got the early train.

I ask the conductor, and he's all irritated I didn't stamp my ticket in the machine at the station. Tells me I need to change trains at Utrecht. And stamp my ticket there. Be sure to stamp.

OK, ok.

Off the train at Utrecht, there's the Schiphol one marked for quay 7. This is 5. To the right, quays 1-4. To the left, 8-12. Seven, please. Neither right not left leaves the middle, and the train at the opposite quay, not quay 6 but indeed 7 (what do they have against 6? there are other even-numbered quays), is just leaving... Ah, there is another train farther down quay 7, and it is the right one. Leaving immediately.

Ooh. Good thing I decided not to try and get a coffee.

I haven't completely figured out Dutch trains yet. Very helpfully, a screen on the train from Nijmegen told us what the stops where and when we would make them. Close to a stop they display what connections are leaving soon. I was relieved to see my destination, and doubly so on seeing a time 40 minutes later. If I'm going to spend 40 minutes in Utrecht waiting for my connection, thank goodness I took the early train. On the later one I'd miss my plane, or be so stressed about it I might as well. That's why I thought I had plenty of time to get a coffee. But when I saw the train, and the imminent departure time I was lucky to hop aboard in time. Was 40 minutes for the next one? Or did 10:30 refer to our arrival time at the airport (and we do arrive at 10:30) Bit of a difference.

Everything was fine. Nobody looked at my unstamped ticket. The airline was not on strike. There are multiple Starbucks at the airport, on both sides of the security check.

J+117

Un jour, c’est comme si un couteau a été retiré de la plaie. On se sent tellement bien. On peut commencer à cicatriser, finalement.

Puis le lendemain,

non.

Toujours là.

Ne me dit pas que tu me tiendras courant de quelque chose que tu n’as pas la moindre intention de faire.

False economies

So how’s the stagiaire, you might ask, that girl with the unfortunate timing and worse training ?

We were going to look at the clinical data for her samples before deciding which of them to choose to analyse, but ran into the problem that she doesn’t have with her, and cannot get access to, the clinical data (the f*? can’t someone email her a list? – is there no list?) So we have to be satisfied with the labels already assigned.

The problem of how to pick which ones to analyse has been very simply resolved. It turns out that most of the 300+ samples she brought with her are completely degraded and cannot ever be analysed. Only about 60 actually contain DNA in fragments long enough to do anything with. So we’ll go with the 60, whatever they are.

300 blood draws, and 240 of them are good for the trash? What happens when you don’t make the necessary investments up front, but try to get by as cheaply as possible. Instead of using some modern but relatively expensive kit for extracting the DNA, they used the tried and true phenol-chloroform method.

When I was in grad school, a wise post-doc always said “The fast way is the slow way, and the slow way is the fast way.” Very good advice, that. Same can be true of expensive and cheap, when cheap puts success at risk.

Now, you can get acceptable DNA with this method, but you have to really know what you’re doing. This is the method I used way back when I was a tech, and it was not always a success. The first thing to do was to get your reagents right, and that meant spending all the necessary time under the fume hood buffering the phenol to a neutral pH. No neutral pH, no good DNA. Just forget it. Whatever comes out might look good at first glance, then fall to pieces over the next week or month, leaving nothing.

Once you’ve got your phenol neutralized, and you extract the washed white cells from your blood, recover the aqueous phase, re-extract that twice with chloroform to get the phenol gone – and a third time if needed. Yes, just do it again. Phenol is the kiss of death for any further manipulation. Chloroform just evaporates no problem. Now you can precipitate your clean(ish) DNA with ethanol and just a bit of salt if there isn’t enough already. But don’t spin it down. Nice DNA will form a beautiful, fluffy white cloud, like magic, as soon as the ethanol hits it. Seal the end of a glass pipet (ooo yes, get to play with fire in the lab!), and fish the blob of DNA out (do let the pipet cool before dipping it in – otherwise the ethanol at 60% will ignite). Squeeze the DNA blob like a sponge against the edge of the tube and once the ethanol has evaporated, swish it around in a tube of aqueous buffer and let it resuspend for a couple of days before attempting to measure its concentration.

So our student is working on the samples that can be worked on, and we’ll see on Monday what sort of results can be had. Cross our fingers that once she passes the preliminary amplification step, all the rest is ok. After all, the rest all works off of the product of the first step, not the primary material. Because if there are no results, um, well there really is no plan B.

Nijmegen

Off to Holland on the early flight, then a proper train through such places as Utrecht and Arnhem. Last stop: Nijmegen.

I bring the camera, hoping to have some time to poke around Nijmegen, one of the oldest cities in this country, between sessions at the A-T meeting I've been sent here for. Alas, our hotel is several km outside of the city, in a modern university suburb. Neat & tidy, but boring. The area is nicely wooded and surprisingly hilly for the Netherlands. The hotel brochure mentions a 60 minute walk and a 90 minute one, and even a 16km connection to some sort of national trail network with no proposed timing. Hah, guess you can get out for a walk if you want to.

Ah, here's the meeting schedule. Everything's over with lunch on Saturday, and as long as it doesn't rain I'll have that afternoon to stroll around the autumn hills of Holland. Fingers crossed that the weather holds, because it isn't looking good.

I haven't been to an A-T workshop in ages. The APRAT, the local family association, holds a meeting every two years or so, and I do see one or two of my old colleagues at those events, but they're mostly for the families, not for scientists. They talk about daily issues - how to get the help they need, how to deal with school and physical therapy, tricks to keep their kids involved and active and as healthy as possible. They want to know about treatment, and what to expect of the future, but not too much.

This is a clinical meeting set up to talk about all the nitty-gritty and what can be done and what isn't working and what might eventually be a good idea. I'm here to distill all that into a progress report for the families in France. I hope there's good news. Something to say that they haven't been saying for years already.

There's a slide put up showing the increase in life expectancy for the general population over the past century, showing also the life expectancy curve for people with cystic fibrosis. CF is another recessive genetic disease for which the gene was cloned some several years ago but like A-T that did not particularly help in developing a cure for the illness. The CF curve is going up, though, faster than that of the general population. All the increase is linked to better everyday symptomatic care, and to being pro-active and staying ahead of problems before they're intractable.

At lunch, the father of two A-T patients said to me that he didn't think the curve for A-T patients had changed at all, in spite of all our meetings and networks and expertise.

I thought this just couldn't be true. Like CF, A-T patients are treated as their problems come up, with a recent accent on keeping ahead any bug to settle in the lungs and on exercises to keep the functions that one has, or at least lose them more slowly. So we must be doing better even if there's no cure for the fundamental problem. So I asked around, because these are just the people who would know. But the ones I asked didn't really know. Though they did suspect the father was right, and the survival curve, if it had improved at all, had done so very modestly. Not like the CF curve.

It's actually complicated to figure. In the past decade, lots of patients with variant phenotypes, all mild, have been found to have A-T, genetically. They have real deleterious mutations, just not the severe disease course. So the overall survival figures are inflated by the inclusion of these milder cases (or, conversely, the disease is being redefined). If you stick to 'classical' A-T, and people are increasingly careful to preface their talks with that word, then nobody has the numbers.

Any improvement is not very big.

Which is odd, because if we have better antibiotics, or at least a wider variety of them, and we know better how to do physical therapy (and when), and we're better at chemotherapy, then there should reasonably be some improvement. There are more anecdotes today about A-T patients in their 30s and 40s than there ever were - do they not shift anything?

We talk about health risks in heterozygotes. The cancer risk pretty much boils down to breast cancer in women, which is well-studied. The small residual increased risk for A-T parents to die of cancer is spread out over all types and ages, and there's nothing to follow up on there. The question today is how to catch the breast cancers early, and if the standard mammography might be provoking years later the very thing it's meant to detect. Scientifically, that would make sense. But because of the delay between starting screening and detecting a cancer, nobody can say for sure if the radiological screening itself increased the risk. So women are still being referred for mammograms as early as age 40, and we will see in 10 years if we've made a very big mistake. Or not.

There are other health problems in the carriers. Heart disease, diabetes, things that don't appear to have much to do with the gene defective in A-T.

Why heart disease?

Well, most of the known and studied carriers are the parents of patients. These people have a lot of stress, from caring from their chronically ill children, even more so when their kids become adults with less and less autonomy. And they tend to neglect their own health. It isn't because they have just one working copy of ATM. They have Caregiver Syndrome.

I don't know if it's an official syndrome, but it could be.

If you could get the non-parent carriers in a study (the brothers and sisters and aunts and uncles...) and follow them up long enough, you'd probably confirm this. And then all the carriers identified through the breast cancer risk cohorts - they have no A-T patients in their families at all. Do they have these same problems?

Anyway, it's an interesting meeting, which goes past far faster than I can write about it.

Friday evening there's a bus to take us into town, for a quick private tour of the museum and dinner in one of the historical buildings.

At the museum we skip the extensive temporary exhibit of fashionable hats. Ditto the installations of multimedia modern "art" (thank goodness). We tour instead the history of the city with its Roman camps and strategic positioning on a low bluff along one of the major arms of the Rhine delta. This was the northwestern edge of the Roman Empire.

Yeah, who'd'a thunk?

(Well, ok, anybody with a decent idea of European history)

There used to be interesting castles and forts around, but they've mostly disappeared. Often used as sources of ready-quarried stone or free bricks, and prominent buildings remaining from the middle ages were flattened in a mistaken but very efficient bombing run by the Americans in 1944.

The museum closes at 5 sharp, and we're told by our hosts before being ushered outside into the early night that we're welcome to gather even now at the restaurant for drinks, but at any rate please be there by 6:30 for the meal. It's right down the street here, then on the right. Can't miss it: it's the only "old" building on the square. Shops close at 6 if you're going to wander around town.

Shops close at 6? Dinner at 6:30? Thank goodness they pushed the schedule back half an hour - the program says dinner at 6, and I don't think anyone but the Dutch in our group is interested in eating so early.

I head off with my friend Janet, whom I haven't seen in years, since another of these A-T workshops. The buildings are typical brick rowhouses, three stories tall.. The old street surface is brick. The shops on the ground floors are just the same ones now that you find all over France and the UK, just about. Seems you could be anywhere. The eateries are mostly local, though there are a lot of chain restaurants and fast foods coming in. More homogenization.

Janet exclaims There's a Hema! Just the place to get decent(ish) stuff really cheap. Hema hasn't made it to Clermont, or apparently to Lyon where Janet is based, but Paris has them. The deli section has all sorts of cookies and crackers and sweets and jarred condiments and prepackaged meals, just the stuff an English person needs when in France for too long.

Indeed. I must come back here tomorrow.

Dinner is served at long, long tables in an old merchant storehouse and trading center. Very quaint, lots of wood with iron fittings and brick floors and magnificently high ceilings. Wine from Chile and Argentina, not from any of those little countries right next door.

I used to hate these dinners because I didn't know anyone, and you're stuck there until the bus comes to fetch you. Now I know some people at least a little bit, and I know some of the other people they mention so frequently when talking shop. Which is most of the time of course.  Janet I've known since moving to France, Luciana and our hostess Corry here at my sector of table since grad school, so I'm not so ill at ease. I don't work directly on A-T any more, but it's a good bunch, and the evening goes well.

After two and a half hours at table, though, I really would rather go out for a walk around for the last half hour. It's raining lightly, but what the hell.

The streets are deserted. Many of the shops use metal roll-down curtains, so you can't even look in the windows (not to mention the sad grey air that gives the whole street). The fabulous church is all shrouded in scaffolding. I get as far as the museum, where the bus will pick us up, and it isn't there yet. Curious. You'd think it would be there by now.

Perhaps there's a change in plans and the bus will after all be allowed to pick us up in front of the restaurant, and I'm at this very moment missing that announcement...

So I wander back the other way. Some of my colleagues have gotten their coats and gone for a stroll by now too, and here's Janet and Luciana and a young post-doc. Luciana appears to fear waiting in the drizzle, and looking back toward the museum I see our bus has arrived. If we get on now we can get the very very best seats - the front row on the upper deck. We do that, and save the Italian professor's hair from a soaking.

The thing with getting on the bus too early, however, is that you might end up missing it.

I'm not ready to sit still yet, so while the others settle in I go out again. It's just a few hundred feet through the park to the view over the river with its bridges and houses all lit up. And the ruins of the castle are lit up. Nice. I wander back, all the time in the world,, and see the bus close its doors. Somehow that fails to indicate to my sluggish brain that this means it's about to leave. Time has stopped. They're just closing the doors because it's cold out. What I would do - I'm getting cold.

Yeah, and then it starts to move.

Hey! Wait!

par for the course

For years my lab has been noting/announcing/complaining that we definitely need a proper laboratory management computing system to handle the thousands of samples and tests we do. Things get lost. Mixed up. Set aside. It's hard to handle everything manually when you have some 500 tests pending at any given moment.

Several years ago we did win a grant to develop such a system with a local start-up company, but after a long time of throwing good money after bad, the project was given up as being far beyond the capacity of the startup.
Um, you might ask, might there be any appropriate commercial software available for your problem?
Yes, there is. But for a genetics lab, where we deal not just with individuals with families, and not just the analysis of one little item but a whole chain of items to make a whole, Appropriate Software costs hundreds of thousands of bucks.
Bucks we don't have, and that our computing department doesn't believe we need. They sent us off to develop what we needed on our own!

Then one fine day there was a problem with the identification of a patient (which was in fact not our problem at all, but a problem at the hospital level of the labels they print being limited to a certain number of characters, and a patient with a name longer than that), and the head of computing suddenly decided we needed a proper system for handling all our samples.
A-hah.
And then she decided that we should have this one particular program to do it. Without consulting us, of course. Just happens that this is one of the better systems we've looked into. We were happy enough to have this imposed upon us. Now we're getting into setting it up, and it comes to light that there's a new version coming out in the spring. And that the new version is far better adapted to our needs. So naturally they will start training now & all, but when it comes to the installation we'll get the new version, not the old.
Only, the new version doesn't work with Windows XP.
Why should it? Nobody uses XP any more.
Do they?
Well, um, we do.
And do you think they're just going to install a better operating system on all our machines?
HAHAHAHAHAHAHAHAHAHAHAHAHAHAHAHAHAHAHAHAHAHAHAHAHAHAHA

Mont Dore 2

I set off at 9 for my big hike. Two possibilities, both of which are 15+ km and spend most of that up on the treeless plateaux, hopping from summit to summit. There's quite a wind, so I opt for the one that spends more time in the woods. That's the one that goes by all three waterfalls anyway, and maybe as the day warms the wind will die down.

Nice. A bit dark here under the thick canopy. Next time I will haul a tripod. Really. Breaking out of the protection of the woods after about 4km, the wind has not stopped. It's livable, though. I continue on across the softly golden hillsides toward my first summit, the Puy de la Tache.

The erosion along the trail across this private land is so bad that the trail is cordoned off with fencing on both sides so you can't make new paths. Plus, they've put in steps and drainage canals where necessary. All along the edges are blueberry bushes, ankle-high, naked of any berries and mostly of leaves.

The wind is bad, cursing muttering bad, all the long muddy slog to the top. But once you're on top you realize you've been in the lee of the mountain the whole way. Up on top the wind will knock you flat. It's so strong all my pictures of the fabulous views are blurry from the shaking.

The book says these high routes should be avoided in times of bad weather or strong wind. Yeah. The next 8 or 9 km of this circuit consists of following the ridges from one summit to the next. Every bit of it in this wind.

That's just misery, if it's even possible.

You could simply be thrown off the edge.

Gorgeous views, but I think I will have to pass. I will go back the way I came, then continue the circle backwards from the starting point, hitting the third waterfall, and decide then whether to continue up again to new vistas on high, or to call it a day.

Not many people are out on the trails today. I've passed a handful of cyclists on the roads, and barely a dozen hikers - half of those on the Puy de la Tache deciding like me not to go on.

The path to the Grand Cascade is busier. This is apparently a must-see if you're in Mont Dore, and the way is indicated all over town. Then a bright yellow sign at the foot of the real trailhead: Beware! Difficult climb! One hour round trip!

Guess the locals are sick of rescuing yokels who go beyond their limits.

In fact the trail is wide and only slightly rocky. It's not exceptionally steep, just always, always up. There are benches to rest at, at first. Later, moss-covered boulders abount like so many scattered cushions.

For a hundred meters before you get there, you can enjoy the Dore river run pell-mell down the gorge. And then there it is, falling from the hill above.

Very nice.

I had the other waterfalls to myself, but here's a woman with a dog, and a man posing in the spray zone while his companion takes photos, and a family group of hikers heading down.

The sign says I can go up to a summit for 8 km, or just up to the next pass for 1.2. I'll take the 1.2, see what's up there.

As you emerge from the protected fold of the mountains there are lots of scraggly trees, their trunks and limbs covered with shrouds of grey lichen. The moss is doing very well in the increasingly windy heights, a great springy bed inches thick in some places. It looks so soft and inviting, but it covers a lot of treacherous rocks so if you go off the trail you could easily twist an ankle.

I don't go all the way to the pass. It's just not any fun in this horrible wind. I keep telling myself that only at the pass can I see the other side. Another few steps. Another turn in the trail. How long can 1.2 km be? Eh, feckit. The other side is just like this side, with even more wind. The sun is gone anyway, too many clouds.

So I go back down.

I'd like to poke around the shops in town, just to pass the end of the afternoon. Maybe pick up a clever t-shirt or some unusual jam. But Everything is shut. Nobody is around. Okay, there is one place open. Exactly one, and unless you're into hearts, it's disappointing. Hearts, they have. Stuffed, ceramic, glass, fabric. On mugs, aprons, ornaments. Time for a shower.

The town is so closed I'm thinking pizza by default, don't even look elsewhere. Unless they too are off to honor November 11. But on entering my hotel, I see the sign with what's for dinner has been changed in my absence. Forget ray with cheese. Steak with blue cheese sauce. My kind of post-hike meal, and I don't even have to go outside for it.

Which is a good thing, because later it begins to rain. I will just stay in with my books - one to read, one to write, pile all the pillows together, and pass the time.

Back to Clermont Wednesday morning to play cards with Michèle. We're playing a competition at the end of the month, the Women's Pairs, and need to get some practice time in together. We start off well, then crash and burn for an overall 47%. Not good. We'll have to work on communication before the 30th.

Le Mont Dore

Here I am again, hopping a train to Somewhere Else. Only it's a bus. Why isn't it a train? There is a train that goes there. I prefer trains - they're easier to write on (no, not write on the train; I'm not a vandal - writing in a book while sitting in a train). On the bus you have to wait for it to stop, and what can you say in just a minute, or the few seconds of a red light?

The bus is filling fast. Who knew Ussel was such a popular destination? Though perhaps everyone is getting off at Laqueuille, like me, to head to more mountainous places, like Mont Dore.

Why not Mont Dore, for a bit of late-season hiking? The weather appears cooperative, at least for the day, at least down here on the plain. Up there I could be up to my ankles in mud, the wind howling past my ears, the countryside grey and sodden and not uplifting at all. I'll take the chance. I could use a bit of uplifting, but if I end up wallowing in sorrow and regret, well, whatever. You roll the dice, you get what you get.

The sky starts out brilliantly blue, and the all leaves shine golden in the low sun. Perfect. But as we climb out of the plain de Limagne, the clouds accumulate on the heights, the temperature drops and the wind comes up like a whip.

Changing 'trains' in Laqueuille I'm glad to just get onto the new, empty, bus instead of poking around the deserted station. Such courage. Bodes well for the next couple days. The windows on one side of the bus are dotted with raindrops.

Happily, the gloom appears to be a Laqueuille thing, as I've seen before passing through here. A microclimate that keeps the grass green to keep the cows fed to keep the blue ribbons on the excellent blue cheese. Once in Mont Dore the clouds aggregate into groups and blue spaces. If I'm patient, the pictures will be nice. Blue all day would have been too easy.

Le Mont Dore: spa town and ski station in the minor mountains. Half closed today. Too late for summer hiking, too early for the skiers. Once the Toussaint school holidays are past, people shut up shop for the rest of November and head to Morocco or Tunisia for a bit of relaxation before the winter sports season.

A bar-café is open and nearly empty when I set my bag down at a corner table by the door at 12:15. Before my ham & cheese crepe is delivered, the place has filled up and they're turning people away. Come back in an hour. This must be the only lunch place open in the whole town.

What I really want is a great bowl of spaghetti bolognaise. Maybe tonight - there is an italian place up the street open only for dinner. If they're open at all.

Yes, again. Table for one.

Ca était, madame?

Oui, très bien.

Dessert? crèpe...?

Crèpe

Au sucre? confiture? ... myrtille...?

Ah, myrtille!

Blueberry. Possibly, it won't be from a gallon jar, but home-made, local berry blueberry jam. One can dream. Seriously, they could really serve homemade. Everybody makes jam around here.

Indeed it is. More sugar than I would use, but lots of real blueberry flavor.

Eventually I liberate my table to the benefit of further hungry visitors. Mont Dore is not so deserted as that, but in the paradox of the off-season it can be harder to get a table when there's little competition than when there's lots.

Drop my stuff off at the hotel, and I'm out for a walk. Tomorow I'll take the 16km circuit around the three waterfalls and the top of the wind-blasted plateau. Today I want just a warm-up. How about a wander around the proliferation of mountain bike trails from here to La Bourboule. Sounds good. Doesn't matter if I get anywhere, just that I don't get so lost I'm not back to town by dark. Wouldn't want to break an ankle or anything.

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It's wet here in the underbrush. Seriously, long-term wet. Maybe there was a dry day back in July. The moss on the trees goes all the way around. It hasn't rained since at least this morning, perhaps yesterday, and yet the foliage overhanging the trail is still dripping.

Walk and walk and walk, just me and my thoughts. I told my friend M, when she asked if I would like to play the tournament in Thiers tomorrow, that I was coming up here for some hiking with a friend whose cousins live nearby. They do, and another time this might be true, but J is at work today. I really wanted an ordinary prior committment. No way am I playing cards in Thiers tomorrow. But no way do I want to explain that 2 days wandering the heights alone is a proper thing to do.

Sometimes you just have to get away from the well-wishers and the real friends yes but for whom human company is always better than none.

No, it isn't.

Some days you just have to go out on your own; give the planet a chance to have a private word.

This is some species of morel mushroom you see a lot of in the markets these days. Would take it with me if I had a fridge handy....

And yet, this travelling solo isn't what it used to be.

Used to be, I'd head off looking forward, noticing the clouds and a flock of birds and the fallen leaves on the trail. I'd just go, and I didn't mind dining alone.

But now, I keep thinking how lonely being alone can be. How nice it would be to have a special companion to recount the day's adventures to on arriving back at base camp, or better, to share them in the first place. Look at those birds!

A perspective irrevocably changed.

He, of course, is not alone, and will surely be playing bridge in Thiers tomorrow. For a pleasantly shared experience.

I should lay in some kind of snackage for my hike tomorrow. The guide book says it's a 6-hour trek, though I'd say less than 5 even with generous stops. That's five hours away from anywhere to get lunch. And I like a bit of lunch.

As I have noted already, this town is half closed. No bakery open, convenience store says back in 4 weeks. Finally a shop open - where do the locals go? Must be a big grocery store down the road a ways.

Five iffy clementines and a package of chocolate chip granola bars. They'll hold me over.

I could have reserved dinner at my hotel, but then noticed the menu - wing of ray with St Nectaire.

Um, fish... with cheese.

N.... no

Let's hope the pizza place up the street is not on vacation. I spied lasagna on the menu in the window, and I've been craving lasagna since yesterday.

Yesterday. 2nd round of the Open Pairs for my level of player; M and I were 18th after the first session. A long way from the top 7 needed to advance. The cold sandwich in my bag really didn't excite me, but happily we found a little bistro to ask nicely if we could eat our own meals there, and they said ok so M was happy and I saw steak & fries on the menu and my sandwich remained uneaten.

Gotta have something hot on a cold rainy day. You want to move up 11 places or not? Let's have a small carafe of wine with that.

So I ate hot food and we had a coffee and got back with five minutes to spare. They only give you about 40 minutes for lunch, and most people just sign up for a sandwich at the tournament venue. In the afternoon we played about as well as we had played in the morning. I never look at our ranking as we go, even though I'm the one keeping score. Knowing jinkes me : if I'm doing badly I do worse, and if I'm doing well I get over-confident. Best not to know.

Really, we played the same. Just as many dumb mistakes and failures of courage and lack of noticing. Same cardsense.

We came up 7th overall.

WTF?

We're going to Grenoble in April.

A hot shower (wow, that water gets real hot if you want it to) and a nap, and I walk back up along the main tourist street with it's 'local flavor' restaurants with their truffades and tartiflettes. All closed. The pizza place farther up is open, though. And they have an edible, molten hot, lasagna. If nothing else is open tomorrow, I'll come back for a pizza. Though a good tartiflette would be nice... No worries - they probably make tartiflette pizza here.

Warning: snarkiness ahead.

It's probably not a good month to be my stagiaire. 

On the surface: calm, subdued, not at all excitable.

But just scratch a bit, and PAF.

Case in point - you would expect a third year graduate student studying the involvement of the BRCA2 gene in hereditary breast cancer would have some idea of what hereditary breast cancer looks like. That's easy. It happens early, happens to close relatives, and is often accompanied by ovarian cancer. You can hardly navigate the BRCA literature without being beaten over the head with this, and you might be incited to include prostate and pancreatic cancer as part of the spectrum.

So the student shows up with a bunch of samples - 40 familial, 200 sporadic, and 150 healthy controls to do a case-control study to see if BRCA2 is involved in familial breast cancer in Tunisian women. As if the thousands of papers on the subject from all over the world - including Tunisia - did not already show that null mutations in BRCA2 are associated with 10-fold breast and ovarian cancer risks, and that neutral polymorphisms are just that - neutral.

Well, if she's here to reinvent the wheel, at least let's make sure it's a round wheel.

How were the familial cases chosen?

They're familial.

Yes, but what criteria did they meet to be defined as familial breast cancer cases? (Age at diagnosis matters, as does the degree of relatedness between affected relatives.)

Um, we asked the case if she had a relative with breast cancer, and we put it into a computer program that told us more than 50%.

Ah. What computer program was this ? (there are several commonly used)

Ummmm.

So much for the familial cases. What about the sporadic cases? 

They're not familial.

Yes, but did you assign a cutoff for age at diagnosis? Did any of them have relatives with ovarian cancer?

Huh?

Not only doesn't she know, but she doesn't think it important to know. Has she read anything at all? I don't even get into the control samples. In a case-control study you really have to vet the controls and be sure they represent the absence of what you're looking for in the cases - a control with two sisters sick with breast cancer is not a control here. Plus, if your controls don't have breast cancer but they're only 30 years old, well, that's not any good either when your cases are all 50+.

OK. Here's one of the papers that reviews the BRCA genes and hereditary cancer risk. It has a handy table in the back that we use to quickly score families for the likelihood of carrying a BRCA mutation. How about you calculate the score for each of your cases, and then we'll take a look together and reassign familial versus sporadic cases accordingly.

Uh, I can't. We didn't ask at what age the relatives had cancer.

Great. In the Eisinger scale, only female breast cancer is weighted by age at diagnosis, so if she has the age of the index case, assigning a fixed weight to each relative just according to type of cancer shouldn't get us too far off track.

She's only here for 2 months, which is just time to test about half the samples she brought. So we need to decide which half. The project is poorly designed to begin with, and just cutting the groups in half randomly will exacerbate the effect of mistakes in assigning samples to one or another group. The study can be improved by selecting the real familial case group by applying the Eisinger scale to all her cases, then identifying a sporadic group selected for the absence of an enlarged definition of family history plus age at diagnosis around the average for Tunisia, and then taking only the oldest of the women in the control group (excluding personal or family history of ovarian cancer, though I doubt she has that information).

It bugs me that a 3rd year grad student knows essentially nothing about her subject. What's she been doing for 2 years? Who I'd really like to throttle is her boss, who came up with this nonsense project, who has not insisted that the student read and understand the literature on the subject, and who cranks out lame little papers that give the appearance of saying something when they really don't because the methodology just isn't there.

J + 80

I'll just say this in English because I have a proper mastery of that language and when I say things in other languages there's always some doubt that my failure to use some subjunctive conditional case correctly turns everything upside-down and backwards and uncertainties to either flights of fancy or straw-men where the opposite is understood. Let us establish, just for the sake of current arguments, that the "present" may extend through the near-future of the next couple of years, and the "future" is ten years and more.

You don't know that you're sacrificing my future happiness by being with me.

I do know that your absence sacrifices my happiness today. And that if there is a future, any happiness in it will not now come from you.

Is the future more valuable than the present?

And what of your happiness? Were you happy with me? Are you happy without me?

I will not ask about your happiness in 15 years. You cannot know.
Nobody can.

Yeah, that'll take just a few minutes

F:

So, remember when you argued that the reduced miscarriage rate observed in this one study we did on the breast/ovarian cancer predisposition database might be associated with an increase in the rate of congenital anomalies in the children born to those women? After all, if miscarriages exist in part to eliminate babies with serious anomalies, and mutations in the genes that put these families at risk of cancer have to do with DNA repair, and whenever DNA repair is not so good, you have more mistakes and anomalies, it stands to reason...

Well, there happens to be a large, regional congenital anomalies register that’s supposedly exhaustive, so I called some people up and looked into it.

Turns out, not only do families with cancer risk (any cancer, not just breast cancer) declare fewer miscarriages than usual, but we could match them to the congenital anomalies register and guess what? They have far fewer kids with anomalies, too.

Strange, huh?

But there you are.

So I’ve written up a bit of a paper, and I’d like to get it submitted in November.

N:

Ah, that’s interesting. I’m eager to see the data. Who knew my annoying objections would go so far.

November, you say? Well, I’m away one week in two for the next month...

F:

Well, I’d really like to get it submitted. Perhaps you can take a look at it before you leave.

N:

That gives me just one week. I don’t think it’s going to happen.

F:

Aw, give it a try.

N:

(perusing the manuscript with its 10 pages of single-spaced F-ese) Um, is this first part the abstract? Or the introduction?

F:

Oh, I haven’t written the abstract yet. That’s a sort of introduction. Feel free to flesh it out, maybe add some references. I’m not really a fertility expert.

N:
Ah.
Well. 
I'll see what I can do.

lundi

non, y'a pas de truc
l'amour, la joie, le soleil, retirés de la vie
reste plus rien

Passe aux moyens.

truc du jour, mardi

mardi, mardi, ehhh, bon, il y a toujours le fourrure très doux de Bandersnatch. Oui, et il reste quelques chocolats noir aux beurre de cacahuète de Trader Joe’s. Et la possibilité de bien dormir – je vais tenter ça une fois de plus. Faut y croire.

Plus loin, il y a du bridge. Mais c’est bien loin. Jeudi. 

Pas facile de se projeter jusqu’au jeudi. 

Fear of Happiness

Yep, if it's in the New York Times, it's official.
The fear of happiness is a real thing.
Somehow I knew this. I know somebody with a serious fear of happiness. If only he'd been able to deal with that earlier.
So people: don't say no to happiness when it comes and knocks on your door. Don't tell it to go away, or chase it down the street.
I'm not saying to pursue your personal bliss to the exclusion of other things in your life, or at the expense of others. But when the sun smiles at you, smile back. It's alright to have a little happiness.

Dormir

Je sais qu’un jour, tôt ou tard, je vais bien dormir.

J’adore dormir, et ça m’agace de me réveiller à 3h de mat’ puis rester éveillée jusqu’au 6 à tourner à droit, à gauche, mettre le chat dehors. Je ne veux que dormir 8 bonnes heures, bien tranquilles. Ca m’agace de me mettre au lit épuisée, physiquement crevée, pour ensuite tourner en rond dans la tète deux ou trois heures encore.

Dormir.

C’est trop à demander ?

Back home again.

You heard some about the trials of travelling – suffice to say it was a good thing I left myself Sunday to recover. Did a couple loads of laundry, picked up fresh food for the week at the market, mowed the lawn, trimmed the roses, ripped out the peas, piled the rotten apples onto the compost heap, sorted the mail, and just hung out at home.

But Monday, well, it’s back to WORK. All my work has been waiting for me. Oh, yes, some of it now gets shunted off to the back-up cadre while I’m gone, but she has her own work and 90% of mine is waiting for me. It’s like an anti-vacation, all this catching up.

So I’m plunging in. Things to do every evening of the week, too, except Monday. Meet my cat-guy, apples for M, get to the bank before they close, groceries (catfood! low on catfood!), bridge tonight and tomorrow and Sunday, friends Saturday (with, yes, a bit of bridge in there). And the Rotary on Wednesday.

Thank goodness for the Rotary. I don’t think I even have any friends but one who are not either work-related or bridge-related or Rotary. Or some combination. And bridge, much as I’m a fan (as you can see), all the bridge club people know JP. I can go to my Rotary meeting, and be back to my single-person status of a year ago without much of anyone batting an eye. So, more good acquaintances that proper friends, though that’s coming. I’ll get more involved in the various events this year. There are plenty of them, and they all need organizing. I hate organizing, but I am sure there is something else I can do.

Hopping from one thing to another, I barely have time to sit on my couch and notice how roomy it is, for one person. Now if only I could sleep.

A brief tour of Southern California

 Not too many pix this time around. Been there, photographed that, just not into it. Used to live in one of the middle apartments of this building.

 Used to live in one of these cottages, too. My first home all to myself, not shared with family or roommates or husband. Heaven for a few months, a quiet space to write my dissertation.

 Went to school here, though not in this particular part of campus.

 The Inverted Fountain was shut off for the off-season. It's pretty cool when it's working.

Wendy's yard in San Diego, featuring Colin. The chihuahuas Jennifer and Gustavo are too quick to be captured.

 A bit of San Diego, seen from Fort Rosecrans. Never did walk all the way down to the Cabrillo National Monument on the point, or the tidepools below. It's about 5 miles to get there from Dan's, but the heat this time was just too oppressive - and the one time I did make it most of the way, they rang me up on that phone-thing, said Hey let's go do stuff, and picked me up in the car.

 Some people think it's strange that Fort Rosecrans would be one of my very favorite places in town. I have no relatives buried here, nor any special connection to the Navy. I just like the serenity here. It's so peaceful. So harmonious. That's what I need now.

 Less harmonious are the new flavors of soda available. Bacon - and - chocolate? in the same fizzy drink? This is just wrong.

 The artists quarter in Balboa Park is much the same as it always has been. Some things you can count on.

Like the swings at the 6th Street Park!
No, I did not break another finger.
And that's all.
.