Wednesday, November 21, 2018

Maintaining homeostasis by prophecy

Homeostasis is the idea of an ideal internal milieu for the cells that the body strives to maintain. The idea was initially proposed by Walter B. Cannon and remains a central tenet of physiology. One of the most basic regulatory mechanisms used to achieve this is negative feedback, wherein a change in some important parameter triggers a compensatory response that serves to bring it back toward the optimal level. This entails that for any true homeostatic parameter there should be an ideal set point. However, there are many such systems that will reset the regulation of their parameter either in response to outside stress, or in disease. Many, if not most researchers have had no problem with expanding the remit of homeostatic regulation to include resetting and learnt neurohormonal mechanisms that might anticipate an environmental challenge. But others felt the need to come up with new words to encapsulate these parts of physiological regulation.

One attempt to conceptualise this is the idea of allostasis, or achieving stability through change. Either change in the set point of a parameter, or change in behaviour, and that this could even be done in anticipation of a change in environment. This is different from the classical view of homeostasis where the organism reacts to a change in a critical parameter and strives to return it to normal. However, allostasis is still poorly defined and researchers that use the term do not agree completely what it means. Some see it as an extension of normal homeostatic physiology, others see allostasis as a pathological process. When you see it as pathological it makes sense to talk about the extra energy expended to change and maintain a homeostatic set point at a new level, or the extra energy expended to perform a changed behaviour. To describe this the researchers who see allostasis as pathological use the term allostatic load, or allostatic stress.

Anyway, if we return to the perspective of the cells with a speculative example; A kidney cell cannot sense a change in outside temperature that will lead to increased metabolic rate, that will lead to increased protein intake, that will lead to increased urea production, that will require increased glomerular filtration in the kidney. So, it has developed a brain and a skin with temperature sensors that tells the brain that it is colder out isde. The brain can then tell cells that produce heat to produce more heat to maintain body temperature. The brain can potentially also tell the kidney that it is making the heating cells work harder and thus that glomerular filtration will need to increase in the near future. While, this example is mostly speculation it serves as an example of a mechanism that would be difficult to fit into a classical homeostatic mechanism. Thereby, it illustrates the usefulness of a new concept whereby a kidney cell could develop a prophetic (for other kidney cells) ability to foresee the need increased work in the future.

Wednesday, October 17, 2018

Cell death used to be easy

I was recently happy to be asked to write a chapter about cell death in the new version of the Swedish textbook on intensive care medicine (You'll find the previous edition here we expect the new one to be published in 2019). Touching up on cell death i found this paper where the leaders everyone in the field spell out the latest understanding about different forms of regulated cell death.

When I last read about cell death it was recognised that there were two basic types, necrosis, that is normal cell death, and apoptosis or programmed cell death. I had heard a little about necroptosis, as it was recently shown to be important in the kidney. I also recognised the name autophagy, but rather thought it was something liver cells did in starvation. It still does, but now it is also a general term for a kind of cell death machinery as well.

It turns out there are now twelve types of regulated cell death (RCD), and even the morphology is no longer any indication of the type of cell death involved. Because, as they write,
"Moreover, each type of RCD can manifest with an entire spectrum of morphological features ranging from fully necrotic to fully apoptotic, and an immunomodulatory profile ranging from anti-inflammatory and tolerogenic to pro-inflammatory and immunogenic."
This plethora of mechanisms does rather complicate the understanding of cell death. Especially so as most of the mechanisms can be activated a little bit and then regress, as long as the death threshold has not been reached. And, even more so as they may switch mechanism if you try to intervene against one of the pathways. This is actually one of the major take-home messages of the paper. We have tried a number of different cell death inhibitors that seem to work in experimental systems where the trigger is controlled. However, when we try them out in patients we find that the cells die anyway.

On the other hand, the great number of different mechanisms opens the possibility of an equally great number of new and shiny papers.

Tuesday, October 16, 2018

Monitoring in anaesthesia and intensive care - 8th Hedenstierna symposium

Activity has not been the highest as of late, but now I am back (perhaps anyway). Today I attended the Hedenstierna symposium in Uppsala on the actual 77th birthday of Göran Hedenstierna himself. He attended, as he always does, and he was suitably embarrassed when the whole meeting sang happy birthday to him.

The good thing with having a famous scientist to name your seminar after is that you can attract real top-names from around the world. This means there are ample opportunities to expand your network both in your field and in associated fields. There were the brilliant Göran Stemme, group leader from KTH who developed the microneedles me and his former student Niclas Roxhed wrote about some years ago. Then Michell Chew chewed on about the very current area of using point-of-care ultrasound in intensive care, and Fernando Sipmann simpered (not really) on monitoring the respiration. After lunch, Declan Bates declared a sermon on mathematical modelling that none of us really understood, but it was very impressive. Finally, Marlies Ostermann orated about the actually important organs, the kidneys. She had a hard time convincing the mostly respiratory scientists in the audience that kidneys are quite simple and just the most fun to be had in physiology.

It wasn't really the final talk, there were Johanna Hästbacka from Helsinki who talked on monitoring inflammation, and Emory Brown from America on neuromonitoring, but I had to pick up my dog from daycare and missed out.

Saturday, August 04, 2018

Print mounting

I am on vacation and finally had a bit of time to mount some of my prints, which I am going to hang in my home office. The home office is rather more important as the hospital has decided to remove our offices because there are workplaces at the operating and intensive care departments. That any doctor would have "stuff" or "papers" is apparently nonsensical. The patient data management system is digital now, and thus we do not need papers, and do not need a personal space.

Anyway, mounting prints is almost as much of a discussion point in photography as all the other things. I learnt how I do it from a Luminous Landscape tutorial, but since I mostly mount smaller prints I eschew hinging the mats, and mostly only mount with mounting corners. We will see.

First and foremost we knoll, as we learnt from Adam Savage through We have four prints and five sets of frames, backs and mats. So, we'll have to find a final print somewhere. When we haven't decided which prints to mount it is an idea to get symmetric mats so that we can decide which whether to use portrait or landscape orientation later. If we know which print we will mount, then slightly asymmetric mats with a thicker lower edge is often more elegant. Let's start with the elephant.

Step one is to place the print and fit the mat. An important point is that it shouldn't  move until it is fixed in place, for that purpose we use a weight. A, flat, clean and heavy weight.

With the weight in place we then place the mounting corners. Since these are small A4-size images, they will stay in place using just corners and the mat. Once the picture is securely mounted, we need to double-check that it fits the mat so that we don't find any mistakes after we mount it.

The frames are Nielsen aluminium profile frames that we put together with these simple corner fixtures consisting of a right-angle plate with two set screws and a shim to distribute the force on the aluminium. In addition there are two hanging fixtures to slide in, and fasten with set screws. For now we will leave one side unmounted to be able to get the print in.

Before sliding the mounted print in, we peel the cover off of the plexiglass and place it on the matted picture and make very sure there is no dust in between. A simple dust blower makes short work of any dirt. By now we really should have signed the mats if we wanted to do that.

In order to keep the stack of backing, print, mat and glass in place the Nielsen system uses leaf springs that you push in under the edges of the frame. I tend to use two per side for A4-size prints.

The last step is to put some hanging wire in place. By only twisting one side to start with it is easy to regulate the height when we actually hang the prints. Oh, and that's one, now for the other four, whereof one needs to be selected and printed first.

But, after all that I have more of my own art on the walls, which is nice. Thank you for following along.

Monday, July 18, 2016

What makes a scientist?

@RealScientists is a scientific outreach Twitter-account that invites a new scientist to talk about their research every week. It is good fun and often very interesting including everything from actual details of data collection in botany and astronomy, to work/family-balance and career planning. Recently, @drclairemurray curated the account and asked the question:
Which was followed by a barrage of answers. Most of which wanted to set the bar really low so that curiosity alone would be a sufficient characteristic. I would rather we set a higher standard so that scientist is something you can strive to become, and have to strive to remain (although often I would like it to be easier).

From this perspective I would like to argue that scientists are like football players. As long as they continue pursuing their own original research and publish with peer-review as the lead or senior author they are still scientists. This is a high bar, and there are some points in this argument that warrant a bit of an explanation.

1: "continue pursuing" means that as soon as they quit actively doing research they also stop being scientists.

2: "their own" means that if they don't provide substantial intellectual input to coming up with the idea, designing and performing the work, and interpreting the results it does not count. This does not mean it has to be only theirs with no outside input, which would be silly.

3: "original research" means that it should be providing either new data, or new interpretations. Experimental reproduction counts, pure theory too, even meta analysis is alright.

4: "publish with peer-review" means just that. The results have to be double-checked by experts and have to be made available to everyone else both now and in the future through publication. This can mean that a bachelor thesis is an adequate start.

5: "lead or senior author" means that they should be the driving force behind publication. The actual position in the author list is not important for the argument, although it is very telling in a field like medicine.

We should, however, be aware that there is an argument for setting the bar low. If they get to identify as scientists already when they do their first experiment and continue to as long as they think rationally, maybe it would be easier to recruit new researchers; maybe the anti-science attitude in the society would decrease; maybe rational thought would be hip again.

Wednesday, June 29, 2016

Widefield astrophotography setup

After posting a snap of my new widefield astrophotography setup on Facebook there was a question about how it was mounted. I thought that if there is one who is interested, there are probably more people out there considering similar questions. Thus, we will take a quick look at a way to mount a widefield camera and a guide camera side-by-side on the Sky-Watcher HEQ5 german equitorial mount.
The Samyang 135mm f/2 manual telephoto lens is an excellent widefield telescope, or so the forums say. It is a super-fast 67.5mm aperture telescope at f/2. We find it mounted on my modified Canon EOS 600D with a Baader Planetarium UV/IR astrophoto filter instead of the normal IR filter. In addition we can use the brilliant clip-in narrow-band filters for H-alpha, OIII and SII to get some of the functionality of a proper astronomical CCD camera. To this we add the 50mm Orion guide scope with a StarShoot autoguider.
The autoguider is mounted on an accessory bracket with a block for mounting on photographic tripods that has a standard tripod mounting hole on the bottom. The bracket and mounting block came with the telescope. Then we can just screw the camera and guider to either side of a standard Vixen dovetail bar. Finally we mount all of that ontop of a computer-controlled Sky-Watcher HEQ5 because: Stability!

Transit of Mercury 2016-05-09

The transit of Mercury happened! Luckily I could escape a little bit early on transit day and set up the telescope to catch us a transit. We see that the gear is a fairly basic set up based on a Sky-Watcher ED80 equipped with a neutral density photographic solar filter from Baader Planetarium and a Canon D600.
Although the day was a partially it worked out well with only the smallest bit of patience. Plus, some clouds are nice to have to cool down a little bit. The mount is a Sky-Watcher HEQ5 that, although it warns us never to point the telescope at the sun everytime we turn it on, can be easily set to solar tracking speed.
In the end I got a little bit sunburned and Skrållan, my then 9-week-old boxer puppy, found a bit of shade by the photo bag.
We saw the whole picture at the top of the page with Mercury to the left and a couple of sunspots in the middle. Below we see two 100% close-up cropped frames to get a better look at the details. The difference between sunspots that are irregular and are surrounded by a lighter penumbra, and the silhouette of Mercury that is perfectly (to the limit of the camera) round and smooth is easy to see.