Showing posts with label Usable News. Show all posts
Showing posts with label Usable News. Show all posts

Saturday, December 11, 2021

Cooking With Solar

Who knew cooking with energy from the sun would be so difficult?

Cooking with rays from the sun- what could be more delightful, or more efficient? The same rays that warm the skin can heat food as well- one merely needs to concentrate the heat a few fold. Well, doing so is remarkably difficult to do in practical terms. Not only do you need to concentrate the sun's heat, but then you have to preserve the heat you collect, without blocking out the light with all that insulation. This can be quite a trick. Thermostatic control? You must be joking- none of the currently sold or proffered DIY projects incorporate such an extravangance. The current state of play is a slightly demented world of youtube videos, fly-by-night companies, and charitable efforts pointed at developing regions. But rest assured, it can be done.

Naturally, the most significant drawback is that the sun doesn't shine all the time, confining solar cooking to mid-day times, and sunny conditions. Several kinds of cookers have been developed, each with individual drawbacks and features. 

  • Parabolic stove
  • Vacuum tube oven
  • Closed box oven
  • Open panel oven

First off, the parabolic solution puts the premium on power. While the other cookers are akin to ovens, this one is more like a range / stove. It gets extremely hot and cooks in a hurry. The concentrated light from the sun needs, however, to be constantly tracked and aimed at the pan on the burner. Yet it is an invisible flame, presenting some difficulty. It can burn a finger or blind you in an instant. One company developed a reasonably practical design, complete with glowing video. But then it promptly shut down and disappeared, I assume due to the daunting legal liability implied in selling such an appliance. These cookers remain very much a DIY, and at your own risk, proposition.

A parabolic cooker- adjust often, and use with care!

Second are vacuum tube ovens, which are basically thermos bottles with sun-facing inputs. These have outstanding insulation, so they capture the radiation coming in very effectively, storing it as heat. They can be used in cloudy conditions and maybe in non-mid-day conditions. The downside is that the thermos structure limits capacity for food, and also hides it from view. These also come in water-heating versions, filling a core camping and emergency need.

A vacuum tube style of oven. This one has quite high capacity. The central thermos provides extremely effective insulation, collecting every bit of the insolation.

Third are closed-box ovens, which are perhaps the most widely used form of solar cooking. Given enough insulation and a well-sealed glass top, you can make a reasonably practical oven out of cardboard boxes, wood, or metal, which get up to 350 degrees °F. This is a slow kind of cooker, perhaps more like a crockpot than an oven, taking quite a bit of time to heat up. They are not so sensitive to light direction, so can be left out for lazy afternoon and will still work. This is an amazingly active area of DIY activity, with endless variations. One of the most impressive I have seen is a sleek, low oven build of glass and wood, meant to stay outside full time.

 A commercially made box oven, with glass top and room for one or two pots.

A DIY version of a box oven, with clean lines and very high capacity.

Lastly, a more portable version of a solar oven is an open panel oven, where a set of foldable or collapsable reflective panels surround the pot, without much other structure. These are maximally simple, and aimed at camping and other portable needs. But they need something extra to hold in the heat around the pot, which may be a plastic oven bag, or a pair of glass bowls that go around the black pot inside. When properly protected, set up, and with large enough collectors, these can get to 300 degrees and work well cooking stews, rice, etc. These enjoy a wide variety of DIY efforts and styles as well, and one of the best is offered by a maker in Southern California.

A panel cooker being used on the go. Note the glass bowl holding the central pot.

Those are the current types, each with its pluses and minuses. Once one considers solar cooking, it is natural to want to deploy it to those who really need it- the rural and poor around the world, who have lots of sun, and not many other resources. The scourge of traditional cooking fuels in these areas is particularly alarming, usually being wood, coal, or dung, which lead to deforestation, climate change, land depletion, and copious pollution, both indoor and outdoor. Thus solar cooking becomes another sort of colonial dream foisted on the less fortunate, who have not set up proper infrastructure to pillage the earth and pollute the atmosphere. But the various impracticalities of solar cooking, including inconvenient timing, outdoor location, low capacity, slow speed, unusual, non-local, and fragile materials, have doomed such efforts to marginal effectiveness. Maybe some further leap in the technology, like incorporating a heat storage mechanism (rocks?) might solve some of these problems. It is amazing, really, how convenient the stored /reduced forms of carbon (in biomass and fossil fuels) are for our needs, and how hard they are to replace.


  • Shades of WW2: All Russia wants is a little elbow room.
  • The gravitational wave observatories are running, and recording the death spirals of black holes.
  • The next presidential election could start a civil war.
  • Carbon tax, now.
  • Good sleep, good life.

Saturday, March 13, 2021

Transmission of SARS-CoV2

Reflections on viral spread.

This is a brief update based on studies of SARS-CoV2 transmission over the course of the pandemic. They mostly nail down features that we already know, and offer a comparison with influenza, which has interesting differences in its transmission. One observation is that influenza has been eradicated to an astonishing degree by our efforts to prevent SARS-CoV2 transmission, a testament not only to the lower transmissibility of influenza, but also to the regular round of death and illness that we have been putting up with for millennia without much complaint.

After all the hand-wringing about hand-washing, we gradually learned that this new virus is almost exclusively passed by aerosols through the air, with limited range in space and time. Also that, despite the infinitesimal size of the virus, that face masks of many kinds are effective in knocking down both emission and reception of viral innocula by several-fold. This is doubtless because both the viruses with their lipid coats, and the moist aerosols they reside in, are quite sticky, prone to capture by even rough cloth filters with channels many times the size of a viral particle. The notorious superspreader events are characterized by 

  • indoors, close physical proximity to others
  • limited air circulation
  • an infected person, typically asymptomatic, engaging in
  • vocal activity, like singing or loud talking
  • with no mask

Scale drawing of surgical mask fibers, against viral and aerosol particle sizes.

Meditation is not conducive to transmission, nor do most infected people transmit their infection. Superspreaders seem to have a very high viral load in key areas of their vocal or respiratory tracts that leads to abundant aerosol emissions with high viral counts. For recipients, it takes numerous viruses to establish an infection- something like 300 for influenza, and something similar for SARS-CoV2. This is a live virus count, not counting inactive viruses, which are always part of the produced and transmitted population of particles. The reason is probably due to our various innate clearance mechanisms, both physical and molecular, meaning that only one virus may get through to successfully infect someone, out of a population of thousands that that person breathed in. 

SARS-CoV2 transmission vs influenza. SARS-CoV2 seems to survive longer in air, leading to more infections in enclosed spaces. Being outdoors subjects the aerosols to getting blown away, and to purifying UV light. This graph does not show it, but SARS-CoV2 also differs in having high viral loads prior to symptom onset, or sometimes without any symptoms, making isolation and contact tracing very difficult.

Additionally, infection by one or few viruses may present a speed problem, where they can not grow an infection fast enough relative to the ability of the immune system to respond and put out small fires. Only if the inoculum immediately generates a large conflagration (think Molotov cocktail) is the fire department overwhelmed, at least for a few days. This leads in turn to the fascinating prospect of mass inoculation with small doses of the virus. Understandably, this is not a popular idea, with its similarity to playing roulette. It resembles the old-fashioned method of small pox inoculation, which used to be done with small doses of actual small pox, not cow pox as was later introduced by Jenner. 

But it may be a significant explanation behind the enormous conundrum of the low impact of Covid-19 on tropical and low-income countries. These countries (India, Central America, Nigeria) show quite high seropositive rates, indicating wide-spread infection. But their death rates and hospitalization rates are very low, and they have escaped this pandemic with relative ease. While reporting issues and pre-existing immune exposure are possible explanations, so is a possible warmer outdoor culture with lower innocula and lower-severity infections. An interesting aspect of inoculum size is that it can have far-reaching consequences, with lower-level infections leading to smaller viral counts in the aerosols emitted, thereby causing smaller, less-severe infections in the next recipients.

The study of viral transmission and infectivity could have profound effects on how we deal with this and similar diseases, and one has to say that it has been frustrating that our knowledge of it remains haphazard, and has been so slow in coming, with such mediocre experiments, false starts and poor messaging.


Saturday, April 4, 2020

How do we Get Out of Here?

It is hard to tell just yet how the coronavirus lockdown will end. Some scenarios.

With the US having frittered away its early opportunity to contain incoming travel and the spread of SARS-CoV-2, we lost containment and now have an endemic pandemic. Nor are our health authorities pursuing definitive contact tracing and quarantine of all cases/contacts- some regions of the country are even well beyond this possibility. Time lines for the lockdown are being progressively extended, without a clear end-game in sight. Where will it end?

The China Solution
China has done draconian quarantines and close tracking, contact tracing, and isolation. And they have stamped out the epidemic, other than a tickle of cases, supposedly mostly coming from abroad. How ironic, but also impressive. They have used institutions and norms of close social control, sometimes rather blunt and indiscriminate, to get the upper hand over this contagion. The prospects for us doing the same are dim. Neither our public officials nor population have the stomach for it. Thus this is not a realistic scenario as an endgame for the US pandemic.

Slow burn
No, we take a more relaxed approach, hoping that the pandemic will magically recede. But that is unlikely to happen, given the vast reservoir of uninfected people, and the virus's high infectivity. So far, the US has ~300,000 cases, and ~8,000 deaths. Assuming that the reported case rate is one-tenth of actual cases, there might be three million people who have been exposed and recovered, out of a population of over 300 million. Exposing everyone would thus result in roughly a million deaths. This will happen no matter how good our social isolation is, or how long it lasts, because the minute anyone pokes their head out, they will be exposed. Without comprehensive tracking and isolation of cases/contacts, our laissez-faire approach leads to a slow burn (also termed flattening the curve) where our hospitals might be able to keep up with the extended crisis, but we still take an enormous hit in illness and death.

Exposure testing
One supplement to the slow burn scenario is the addition of exposure testing, for antigens to SARS-CoV-2. If these tests were broadly offered, like at grocery stores and by home delivery, we could at least recognize a large population that is immune and thus can move freely, (perhaps wearing a scarlet letter!), helping to re-establish economic and other essential activities. This is like having some amount of herd immunity, without waiting for the entire population to have been exposed. But it would not significantly curtail the slow burn, since we are still unwilling to keep everyone else out of circulation in a comprehensive fashion.

County quarantine
Some areas of the country are doing much better than others, and could set up local clean zones and boundaries. Once cases were reduced to a small trickle, the health departments could do what they failed to do at the outset, which is to block and test at all borders, and comprehensively trace contacts and enforce isolation internally. Given the large and necessary traffic of deliveries of goods, especially food, this is quite unlikely to happen, and would represent a sort of breakdown of our political society. But the behavior of the Federal administration, giving a "you're on your own" message to states and localities, does make this scenario more likely. It also ends up being a sort of slow burn, since any locality can not forever keep up such isolation. It would have to continue until the advent of a final solution- a vaccine or treatment.

Vaccine or treatment
This is the magic solution everyone is waiting for. The antivax movement isn't looking so good at this moment,when everyone's attention is focused on virology, epidemiology, and public health. Candidate vaccines are easy to dream up- any protein from the virus could be expressed in some heterologous system (like in E. coli cells or yeast cells) in massive amounts, and injected into people to generate immune responses. But effective vaccines are another story. Coronaviruses and other respiratory viruses tend not to generate strong and durable immune responses. That means that their ingredients just are not that immunogenic- they have devious ways to hide from immune surveillance, for one thing. Indeed, we still do not have good vaccines (or treatments) against the common cold. So a good vaccine will need to use all the tricks of the trade, such as multiple protein pieces, both invariant and variable, and immune-stimulating adjuvants/additives, to make an effective vaccine. It may take a year, but it may also take several years.

It looks like we will be in this lockdown for a very long time, with reduced economic and social activity. And the more effective our social distancing, the longer we will have to stay isolated, as the flatter curve extends out in time. If we go down the China route with more draconian methods to stamp it out before it burns through the whole population, we will be in a very precarious situation until a treatment emerges, given the wide-spread, now endemic, presence of this virus world-wide if not in continuing hot spots in the US.

  • For those locked in ..
  • How China is controlling spread while getting back to work.

Saturday, March 14, 2020

Coronavirus Testing Update

A review of how testing is done, and where we are at.

We in the US are flying blind through the current epidemic, with cases popping up all over, testing done on very few people, and the rest ranging between nervousness and panic. What is the death rate? We still do not know. Did China contain its outbreak by draconian measures, or by wide-spread infection and natural burnout? How about South Korea, or Taiwan? Everyone claims the former, but it far from certain what actually happened. We need more testing, and particularly scientifically sampled population testing, and post-infection exposure testing. The basics of epidemiology, in other words.

SARS-CoV-2 is the virus, and COVID-19 is the disease. Most people do not seem to have mortality risk from infection, other than the elderly and infirm. In these respects, and in its great infectiousness, this disease resembles influenza. Testing from patient samples is done by RT-PCR, which stands for reverse-transcription polymerase chain reaction. The reverse transcription part employs specialized enzymes to copy the viral genomes, which are RNA, from the patient sample, into DNA, the more stable molecule that can be used in PCR. And PCR is the revolutionary method that won a Nobel prize in 1993, which uses a DNA polymerizing enzyme, and short segments of DNA (primers), to repetitively (and exponentially) replicate a chosen stretch of DNA. In this way, a minuscule amount of a pathogen can be processed to an easily detectable amount of DNA. The FDA mandates using three target regions of the new Coronavirus N protein encoding gene for its tests, but will accept one target, if the test is otherwise properly validated. They point test makers to the NAID resource that provides positive control material- RNA genomes from SARS-CoV-2.

 Just the primers, Ma'am. These tubes contained dried DNA- the short primers with specific sequences needed to amplify specific portions of the SARS-CoV-2 viral genome. Using these requires quite of bit of other laboratory equipment and expertise.
Schematic of PCR, the exponential amplification of small amounts of DNA to huge amounts. Primers are in green, nucleotides are light blue, and the target template is dark blue.

So far, so good. But there are a range of test technologies and ways to do this testing, from the bare-bones set of primers, to a roboticized, fully automated system, each appropriate to different institutions and settings. To use the basic primer set, the lab would have to have RNA extraction kits or methods to purify the viral genomes from patient samples, then a reverse transcription kit or method, then a PCR machine and the other materials (nucleotides, high-temperature DNA polymerase, purified water and other proper solution ingredients). The PCR machine is basically a heater that cycles rapidly between the low temperature required for polymerizing and primer annealing, and the higher temperature required to melt all the DNA strands apart so that another round of primer annealing can take place. And all this needs to happen in very clean conditions, since PCR is exceedingly sensitive (of course) to small amounts of contamination. Lastly, the DNA product is typically detected by trace fluorescent markers that light up only double-stranded DNA, and can generally be detected right in the tube, with an advanced PCR machine.

Automated sample handling machines are used in clinical labs.

Virtually all of this can be mustered by any competent molecular biology lab. Results would take a few days, due to the work involved in all the setup steps. The PCR itself and analysis of its results would take a few hours. But such labs do not operate at the requisite scale, or for this purpose. That is the province of clinical testing labs, which come in various sizes, from a small hospital in-house operation to a multinational behemoth. The latter run these tests on a vast, mechanized scale. They might manufacture the DNA primers themselves, or buy them in bulk, and have the proper logistical structures to do these tests from scratch in a reproducible way, to a high standard. Providers at these scales need different kinds of materials for their testing. A small provider may need a turn-key solution that comes with pre-packaged cassettes that just need the sample added before plugging into the machine, while a larger provider would save costs by using bulk reagents and massively robotized sample handling and PCR machines.

A one-hour test in a turn-key package. But at relatively high cost.

So who are the players and what is the status? The CDC did not, for some reason, use the WHO test, or tests already developed in China, whose capacity for such manufacturing and testing is prodigious. The CDC at first didn't allow anyone else to run the tests, and when they did, they did not work correctly. It has been a bad scene and much valuable time has been lost- time that resulted in the US losing any chance of containment. Now, the FDA is authorizing others to run these tests, with detailed instructions about sampling, extraction, and machinery to be used, and is slowly granting authorization to selected manufacturers and kit makers for more kinds of tests.

Large suppliers like Roche and ThermoFisher have just been approved to supply clinical labs with testing systems. Most significant is Roche, whose tests are pre-positioned and ready to go already at clinical labs around the country. The biggest clinical lab, ominously named LabCorp, offers a home-made test, but only "several thousand tests per day", which is not yet the capacity needed. So capacity for testing will rise very rapidly, and soon enable the diagnostic and surveillance testing that is so important, and has been missing to date.

  • Notes on previous pandemics.

Post script:
An aspect I forgot to include is how to select the portions of the viral genome sequence to include in testing kits. Different institutions have clearly come up with primers to different genes, few as they are, and regions within those genes. For example, "The primers currently target the N1, N2, and RP genes of the virus, but these are subject to change."; "In particular, the test detects the presence of SARS-CoV-2’s E gene, which codes for the envelope that surrounds the viral shell, and the gene for the enzyme RNA-dependent RNA polymerase." There is a balance between finding regions and primer sites that are unique to the particular virus you are interested in, so cross-reaction to other viruses is 100% eliminated, and the problem of viral drift and mutation. Some regions of viral genomes mutate much more rapidly than others, but these viruses tend to mutate at pretty high rates overall, so keeping a test current from one year to the next can be challenging. That is also what our immune systems have to deal with, as cold and flu viruses change continually to evade our defenses. So the specific DNA primer targets of a test need to be relatively highly conserved, but not too highly conserved, to put it in evolutionary terms, and the regulating agencies have to keep a close eye on this issue as they approve various test versions, to find a proper balance of high specificity and long-term usability.

Post-Post script:
Yet more significant testing solutions have emerged by late March, including a rapid (~10 minute) system from Abbot, and rapid antigen testing kits that also render results in the ~10 minute range. This speed is enormously helpful, obviously, from the patient, provider, and health system perspectives. The Abbot system is based on something called isothermal PCR, which gets rid of the temperature cycling described above. It is run at an intermediate temperature (~60 degrees C) where the DNA is somewhat loose, and primers can invade duplex strands, and also used a DNA polymerase that can displace duplex DNA as it plows ahead. This plus some other clever tricks allows the DNA amplification process to happen continuously in the reaction tube, going to completion in the rapid time quoted for these tests. These tests also tend to be tough- relatively robust to junk in the samples, and variations in temperature and other conditions.

The antigen tests that are coming on line are particularly significant, since they can be used for wide-spread population surveillance, to figure out what proportion of the population has been exposed, even if no active infection is present. Due to what seems like a complete or virtually complete lack of contact tracing + quarantine, the current pandemic will only stop once most of the population has been exposed, providing herd immunity. Before that point, anytime we give up self-isolation, it will start over again, due to the relatively high rate of low- or asymptomatic cases, and their lengthy course. Health care workers that have been exposed and recovered will have a special role before then by being able to freely staff hospitals that otherwise may be in dire straights.

Saturday, January 11, 2020

Shoulder Rehab for Desk Jockeys

Repair your shoulder and keep it healthy.

This is an unusual post, on self-help. It has been revelatory for me to go through this program, and it might be useful for others who experience shoulder pain, weakness, and lack of mobility. What presents as bursitis, impingement, bicep tendonitis, or even frozen shoulder is often a deeper and more common issue of mis-alignment and weakness in the whole shoulder, with chronic cramping of various muscles, brought on by years of hunching in our modern posture of always-forward attention to computers, phones - even books! In my case it was a lab bench that started the process.

It is hard to get a straight answer or analysis about shoulder problems, since it is a complicated and unusual joint. Small issues in the anatomy can cause big issues with soft-tissue irritation and pain, which may take years to develop, but present as sudden pain and debility. But one key concept is scapular rhythym- the fluid rising motion that the scapula should be following when you reach overhead. That can't happen if the scapula is not properly aligned. Which is to say, it should be flat against the back. When sitting in a chair with a solid back, do your shoulder blades lie flat against it? Or do they stick out against it, or even align to the side, not touching the chair back at all? When standing straight with your hands falling loosely to the side, do your hands face backwards? They shouldn't. They should be facing inwards, to your hips. Bad shoulder alignment affects your whole posture, and correcting it takes time, but yields wide-ranging benefits.

The syndrome is well-described here. Knowing shoulder anatomy is somewhat helpful, but not essential, really. The basic idea of the rehab program is to strengthen the back muscles that pull the shoulder blades back into proper position, after they have been stretched and weakened for so long by the hunched posture that over-weights the front-pulling muscles. The first step is to restore mobility and range of motion to all the muscles around the shoulder. So start with a series of stretches. Older people especially need lots of stretching to keep muscles working properly. Both the stretching and the strengthening would then be a life-long program, given that activities with forward posture tend to also be a life-long love affair.
  • Door stretch: with arms up and elbows half-way up, like a stick-up, lay them against a door frame and push through forward with your body/chest to open up the shoulder and chest.
  • Do the same thing with each arm singly, stretching each arm to 45 degrees back from the plane of the body.
  • Facing against a wall, with one arm, reach straight up, then work the arm back through a full circle, turning sideways and stretching against the wall as you go around. Finish with a cross-stretch with the arm going in the front across your chest.
  • With a broom handle, place it straight up behind one shoulder with the opposite hand, and reach back to it over the top with the same hand. Then pull forward and up with the opposite hand till you feel a stretch in the subscapularis.
  • Brachiation: from a pullup bar, just hang for a few seconds with as much weight as possible.
  • During the day, remember to stand and open up your shoulders periodically. Sometimes you can even get a crack out of your sternum, if you have been hunched for a while. A phone app reminder every 10 minutes may be helpful. 
  • Against a shelf or seat about waist high, lay the front of your arms on it, and lower your trunk till you feel a thorough stretch, then lift about half your weight with your arms- repeat 6 times.
  • Hitch arms together behind your back, grasping each opposite elbow. Bend trunk to the sides, stretching the obliques, bend forward and back. Turn neck to each side as far as possible, holding stretch.
  • With your back towards a shelf or bar about shoulder-high, grab with your hands, and lower your body to stretch the front of the shoulder. The aim should be to get about horizontal with the arms going straight back, or slightly lower. Next, using the same shelf and position, bend each elbow in turn and lay it/forearm on the shelf behind you, lowering the body again. This is a more intense stretch with the same goal.
  • On the floor, on a mat or carpet, make sure your scapula is flat against the ground. Then make angels, swinging arms through full range from sides to overhead, 10X; alternate arms, 10X more.

The next step is strengthening, to counteract the typically forward- directed actions we take all day, and make the posture changes permanent. There are many helpful videos and other instructions on the internet.
  • With face down, on a support like a weight-lifting bench or table, lift the arms straight out and up to the sides, as far as possible. Start with no weights, then add weights as possible. 3X 12 repetitions.
  • Same posture, but with elbows out and arms pointed forward. 3X 12 repetitions
  • Rowing against resistance- using a rowing machine, or resistance band, or rope, pull about 1/2 your weight, 10 times at least. Start slowly with this exercise, as it can cause pain at first.
  • With a relatively heavy resistance band, stretch between your hands in front, about shoulder-wide. While stretching apart as much as you can, work your hands up and down a wall, from arms fully up to fully down, 12X. Start slowly with this one as well.
  • With a relatively light resistance band, extend arms straight forward and pull wide to the sides, out as far as possible, 12X. While you are at it, while extended, swing your arms back over your head and down to your lower back, for a good stretch.
  • With a resistance band anchored to a pole or wall to the side, hold your elbows down at your side with hands straight forward. Pull the resistance band 90 degrees sideways, 20X each direction, strengthening both arms in the rotatory cuff.
  • When all that is working OK, raise weights from the side, standing position, to fully overhead, about 10 pounds each side, 10X, strengthening deltoids.
  • When all that is working OK, add push-ups and pull-ups.

When walking, attend to posture, leading with the feet, not the shoulders. When sitting, attend to posture, laying scapula flat against the seat.

That is the full program, though many other exercises and stretches can be added. Much of the damage and pain from this syndrome can be assigned to the anterior of the rotator cuff, (supraspinatus, subscapularis, and bicep tendon), and this program will not reverse the damage, but it will prevent further damage and allow effective operation of the shoulder without relying on, and irritating, the front of the rotator cuff so much. I think this issue is endemic and under-recognized. Much of the enthusiasm for muscle "trigger points" and deep massage comes from cramped muscles in the shoulder, neck and back regions. But typically, regular stretching is a better and longer-term solution, even if trigger point release provides rapid relief from pain. Every muscle can be stretched, so when you notice one giving pain or limiting range of motion, do some research on how to loosen it up, and add that to your program.

Saturday, August 18, 2018

Blood Tests For Cancer

"Liquid biopsies" for cancer are coming to the clinic.

Cancer remains the winner in the war on cancer. New molecularly-driven precision treatments have improved outcomes for a few types of cancer, and the reduction in smoking has provided substantial improvements in death rates, but the overall statistics remain grim, most treatments are dreadful, and early detection is more a mirage than reality. One promising, though still experimental, area of progress is in detecting cancers using blood samples.

Cancer trends in the US, overall.

Early detection has been a holy grail, with enormous resources devoted to mammography and PSA tests, among much else, which have turned out to be of marginal utility, or far less than touted. I do not believe there is currently any cancer for which a reliable medical test of any kind provides detection before symptoms or manual / visible detection is possible. After the various reliable and unreliable methods of detection, assessment of cancers involves biopsy, which is far more invasive and disruptive than it sounds, piercing the putative site / organ with a large sampling needle which can cause permanent damage. Biopsy should be regarded as a full surgical procedure in its own right.

Both of these problems could be alleviated with effective blood tests for cancer presence, type, and progression. A significant development in the research field over the last decade or two has been the realization that cancers shed material constantly. Cells are sloughed off in live and dead form, and DNA from tumors is generally in circulation. One corollary is that metastasis is more a matter of these cells finding a congenial home than of their dispersal from their primary source. A second is that blood tests can detect these DNAs and cells on a routine basis.

The root method for doing so is PCR- that revolutionary method in molecular biology that harnesses DNA replication to amplify nucleic acids exponentially, allowing detection of infinitesimal amounts. One of the papers under review in this post claims that a single molecule of cancer cell DNA can be detected in 5 ml of blood. This is astonishing, but also puts bounds on the ultimate utility of this method, since they also say that less than half of grade 1 cancers provide even such a tiny signal. It turns out that, as one might expect, earlier and smaller cancers shed less material than later ones do.

Early stage cancers are hard to detect, but not impossible. The lowest Y-axis levels correspond to one molecule in the sample.

This landmark paper tests patients with many different types of cancer to evaluate the possibility of a relatively blood test for certain known cancer mutations. They find that brain cancers are particularly poorly represented- their shed materials are likely to be confined due to the blood-brain barrier system, plus the glymphatic system. But other cancers are quite amenable to blood testing, at least when in an advanced state. This would at least be a boon to recurrence tracking, and treatment monitoring, for which (repeated) biopsy is either impractical or impossible.


Which cancers give usable blood-born DNA samples?

"... 47% of patients with stage I cancers of any type had detectable ctDNA, whereas the fraction of patients with detectable ctDNA was 55, 69, and 82% for patients with stage II, III, and IV cancers, respectively."

For early screening, blood testing is not, as of this paper in 2014, truly reliable. On the other hand, it finds half of stage 1 cancers, which otherwise might not be found at all, raising the question of how such a cancer should diagnosed and found if a blood test finds, for example, that a common mutation (for example, in the gene TP53) is found to be afoot in a patient. Such mutations, which drive many different cancers, could come from virtually any organ. Some more sleuthing would be in order.

One such approach came up recently, in studies of regulatory markings on DNA, which some call "epigentic" marks. C nucleosides in DNA can be methylated and then derivitized from there to 5-hydroxymethyl 5-formyl, 5-carboxyl, and finally identified by the DNA repair pathway and excised / replaced. Typically, methylation is a repressive signal, part of the cellular machinery that turns off gene expression. In contrast, 5-hydroxymethy modified C residues seems to be associated with higher gene expression. At any rate, both modifications are dramatically reduced in cancer cells, and their patterns can be informative about the cancer's tissue of origin and prognosis/stage. There is even the possibility that the relative positions of 5-methyl-C and 5-hydroxymethyl-C in very small segments of DNA (detected by FRET, no less) could be informative on these issues, though that is more esoteric.

So far, these methods are plumbing the blood samples for specific DNA mutations in specific genes known to drive cancer, and thus have high specificity, but limited utility as general screening tools for patients who have not yet been diagnosed and could have any (or several) of thousands of different mutations. To do that, a far larger panel of genes needs to be assayed, possibly even whole genome sequencing, with an unbiased analysis of their mutations. But that begs the question of how to separate the cancer-derived DNA from all the other junk floating around in a blood sample. Methylation marks may be biased in cancer-derived DNA in useful ways, but they do not have categorically different characteristics usable for separating the wheat from the chaff. This is the big problem right now in cancer blood testing. On a practical level, it will start being used for already-diagnosed patients, to track their treatment and relapse. The cancer selection problem will likely be solved in a brute-force way by sequencing everything in the blood sample and sifting through that data using a growing catalog of cancer-causing mutations. But if some mark or characteristic can be found that is specific to cancer DNA, then general and convenient cancer screening via blood tests will come much sooner.

Saturday, May 5, 2018

Green Power

California's open political structure opens the opportunity for the Green party to create a revolution.

A recent op-ed in the local paper by a Republican party official complained about California's open primary system. This system runs primaries and general elections without regard to party affiliation. The top two finishers in the primary run against each other in the general election. In California, this has resulted in many state-wide races being contested between two Democrats. The Republican party no longer has a lock on one position on the general election ballot as they used to, and this naturally rankles. The editorialist complained pathetically about lack of diversity (of all things!), and how the choice between two Democrats was so limited. It was whining at its most exquisite.

California has frequently been in the political vanguard, whether in tax revolts or in progressive climate change policy. The 60s were headquartered here. California has put redistricting on a non-partisan basis. The open primary system has been a dramatic success, giving the best two candidates a hearing before the voters in the general election, and reducing partisanship and cronyism in the state. One side benefit is that voters can register with a minor party without the penalty of being locked out of the key primary races, which are no longer parochial, but open to all. This new political landscape (which was the beneficent and ironic gift of Arnold Schwartzenegger) could lead to another progressive advance, in the form of a revitalized Green party.

Trends in party affiliation in California. Greens come in at 0.62%- currently negligible.

The Democratic regime in California has not been a bad thing on the whole. Under Jerry Brown, who operates as a centrist, the drama surrounding budget battles and other fringe issues has been sharply reduced. Except for the pension crisis, the state has been quite well run, if inefficient. Advances in climate change regulation, marajuana legalization, gun control, and formal resistance to the Trump administration are generally appreciated. Trump is reviled. Education and infrastructure funding remain dreadful. There is little stomach in the state for a return of Republicans as the opposition, (they are now legislatively locked out of veto power), which would bring back endless bickering and corrupt dealing. There is, however, room for less corporatism and more progressivism, which is what a stronger Green party could provide.

The Green party currently is not much healthier than the Republican party, unfortunately. In California, it fields a grand total of 60 office holders, none of which are statewide. Its web sites and organization seem moribund. Due to the two-party structure at the national level, it is unthinkable to support it in presidential races, where it would be a spoiler to benefit Republicans. But with open primaries in California, the party could cultivate a state-wide program and candidates, while vowing to back the Democratic party (or whichever party is more aligned with Green objectives) in races that are significantly contested by Republicans, which is to say, effectively support the left. That would provide a solid platform for activism within the state, building the movement and the party.


Each non-presidential race would have to be carefully evaluated for whether the participation of a Green candidate would raise the chances of Republican / Conservative victory significantly. In primaries, this is likely be a negligible risk as things stand. At least one Democrat will always win in non-rural districts. For the general election, if a Green candidate is not running, Greens would support the Democratic candidate, or whichever one most agreed with the Green agenda. This would make for a sort of mature, parliamentary-style politics, where coalitions are assembled in response to conditions.

Oddly, however, the Green party is officially against the open primary system, mistakenly thinking that the loss of a coveted (though pointless) automatic spot on the general election ballot outweighs the decisive gain of flexibility for their voters and sympathizers in the primary election. They want something still better, like proportional representation, logic that to me seems maybe nice in theory, but self-defeating and irrelevant in practice. Worse, the national Green party is a disaster, indeed a toxic blight on the left, pushing its presidential candidate in the teeth of all logic and experience. That is no way to succeed.

The Republican editorialist bemoaned the lack of competing perspectives and arguments in California politics. But the voters have decisively rejected the Republican program of meanness, business cronyism, labor expoitation, environmental degradation, and xenophobia, which has only become more extreme and blatant on the national level. Maybe the discussion that voters in the state really want is one between Democrats and those who want progress to go even faster- toward single payer health care, faster de-carbonization of the economy, more effective business (and internet) regulation, and more balanced housing and transportation growth, among many other issues. The climate is shifting.



Saturday, August 26, 2017

Mass Transit is Pleasant Travel

Let me count the ways.. I love mass transit.

Love to drive? Some people do. But do you love to drive in LA? The pleasure of driving goes down dramatically in congested conditions, where what was once a carefree sail down the freeway turns into a white-knuckled fight for free space, slowing to a frustrating crawl through a baking, exhaust-filled parking lot. Then there is the fear of accident and injury. Every day, the radio traffic report provides bland "injuryaccident" reports from the metro area. Driving has turned into a nightmare.

The US has not built significant infrastructure, particularly roads, for decades, and it shows in worsening traffic conditions. In parallel, housing prices go up, thanks to an unwillingness to zone for growth in housing as well as in traffic. Yet our population still goes up, despite the sclerosis in public policy. What can be done?

Entering BART trains is easy...

Some urban areas have an answer to the car, and it is mass transit, either by train or bus. The New York subway system ridership has gone up steadily, and is now at 5.7 million per day. The Bay area subway system, BART, has also experienced strong gains, to half a million riders per day. All this despite the growth of ride-share services which, while they may relieve the user of the task of driving, do nothing to resolve the uncertainty and unpleasantness of congestion on the roads.

I have recently switched to transit for a long cross-Bay Area trip, and it has been a revelation. Gone is the road rage and isolation, replaced by abundant people-watching and the ability to just look out the window, or rest (or work). The occasional stress of making a properly-timed bus or train is significantly less than the constant stress of preventing death or collision in a car. Granted, the seats are rarely very comfortable, and not everyone is friendly, or even sane. But on the whole, it is an easy call, especially since the direct costs are almost precisely the same, even before amortizing the cost of the car itself, not to mention those to the planet.

  • Is Afghanistan a satrapy?
  • Afghanistan: rural areas are important, Pakistan is still bad.
  • Pakistan: "Who, us?"
  • Science- broken, or not so bad? And do different fields have different standards and forms of corruption?
  • Our media maelstrom.
  • This just in: insecticides kill insects.
  • Bullies and jerks.. why?
  • Workers will still get the shaft.
  • Russia is still there.
  • How far will denialism go?
  • Environmental graph of the week: California electricity grid during the eclipse. Overall peak demand is about 40,000 Megawatts, so solar generation provides roughly one quarter of peak demand in the state.
The California Electric grid, 08/212017, 5 PM (top), compared to the day before (bottom).

Saturday, June 3, 2017

Massage and the Future of Medicine

Trigger point therapy for muscles. Brief review of "The Frozen Shoulder Workbook", by Clair Davies.

For anyone with muscle issues, trigger point therapy can be a profound experience. This is the palpation, detection, and deep massage of any muscle that has "knots" in it, which are also called trigger points. Such knots can arise from overuse or trauma, and can last for years, impairing use of the muscle, and, in the case of the shoulder, causing a cascade of impairment that comes to be known as frozen shoulder syndrome. Clair Davies' book is a thorough guide through this thicket, and brings to light issues that mainstream medicine seems to be rather slow in picking up.


Indeed, one could imagine that every general physical appointment, which now focuses on a few metrics of internal medicine, such as blood pressure and blood chemistry, might start with lengthy session of skilled massage. This would bring therapeutic massage into the medical setting, where it belongs, relax the patient while attending to key muscle issues that have been building up over the preceeding year, and also provide an entry to many other medical issues the patient may be having, like skin lesions and internal pain.  Something a little shamanic, but also holistic and integrative, changing the medical encounter for the better.