In this episode of the podcast I talk with Ivan Gayton, former mission head at Doctors Without Borders and currently obsessed with placing mapping technology in the hands of the developing world.
If you prefer the written word, you can see the transcript here.
Some highlights:
How Ivan thinks about being fractionally responsible for saving the lives of hundreds of thousands of people, but pretty directly responsible for the killing of 12 (utilitarian deontologicalism, I think?).
Why humanitarianism is a right and a duty, but development is merely nice (humanitarianism is countering the intervention of another human being).
Casually devastating criticism of various international aid agencies (Tanzania is where aid workers go to retire while still drawing a check).
Why accurate open maps are instrumental to humanitarian and development goals in developing countries (contact tracing during epidemics, aid distribution, municipal services, utilities)
How you can contribute to mapping with money or programming talent (especially mobile, Unity or other 3D mapping engines, FPGA, AI, especially for vision, and blockchain). Programming positions are potentially paid, although not at competitive rates.
Links and other references:
Ivan mentions starting his mapping project with Ping. This refers to Ka-Ping Yee, another former co-worker of mine.
In this episode of our podcast, Timothy Telleen-Lawton and I talk to Oliver Habryka of Lightcone Infrastructure about his thoughts on the Open Philanthropy Project, which he believes has become stifled by the PR demands of its primary funder, Good Ventures.
Oliver’s main claim is that around mid 2023 or early 2024, Good Ventures founder Dustin Moskovitz became more concerned about his reputation, and this put a straight jacket over what Open Phil could fund. Moreover it was not enough for a project to be good and pose low reputational risk; it had to be obviously low reputational risk, because OP employees didn’t have enough communication with Good Ventures to pitch exceptions. According to Habryka.
That’s a big caveat. This podcast is pretty one sided, which none of us are happy about (Habryka included). We of course invited OpenPhil to send a representative to record their own episode, but they declined (they did send a written response to this episode, which is linked below and read at end of the episode). If anyone out there wants to asynchronously argue with Habryka on a separate episode, we’d love to hear from you.
4 months ago I described my success curing my hypothyroidism by gargling liquid iodine, when iodine pills had failed. The good news is that the cure has held– my thyroid numbers continue to be in the desirable range.
The bad news is I’ve failed to replicate this success with a multivitamin. Shortly after the thyroid post I was handed a perfect opportunity to put sublingual vitamins to the test when my doctor took me off all my oral vitamins to give my gut a rest. I had already started on EZMelt Multivitamin + Iron (2x standard dosing every other day, because I absorb iron better that way), but now we’d removed all potential assistance (“except food, right?” no. My gut has never been good at extracting vitamins from food except right after I discovered Boswelia. Mold Winter rolled back those gains).
I recently got my nutrition test results back and they suck. I can’t prove I wouldn’t have been even worse off without these vitamins, but there’s a profound absence of positive evidence. However the issue could just be these particular vitamins; after a break I’m now trying Feroglobin, which is a thick liquid iron supplement with a smattering of other vitamins. It’s not intended to be taken sublingually but I don’t live by their rules, man.
Between getting the results and publishing this post I made a market on Manifold, asking whether the EZMelts would work. The market was trading just under 50% “no, not helpful” for most of the week, but in the final hours fluctuated between 30-40% “no”. Seems like a very mild victory for prediction markets.
I’ve created a similar market for Feroglobin here. This run is not going to be quite as clean- my doctor put me back on oral vitamins, plus I finally found a place that does IV nutrition. So this will be more of a best guess, probably resolved as a probability rather than flat Yes/No.
4 months ago I shared that I was taking sublingual vitamins and would test their effect on my nutrition in 2025. This ended up being an unusually good time to test because my stomach was struggling and my doctor took me off almost all vitamins, so the sublinguals were my major non-food source (and I’ve been never good at extracting vitamins from food). I now have the “after” test results. I will announce results in 8 days- but before then, you can bet on Manifold. Will I judge my nutrition results to have been noticeably improved over the previous results?
Timothy and I have recorded a new episode of our podcast with Austin Chen of Manifund (formerly of Manifold, behind the scenes at Manifest).
The start of the conversation was contrasting each of our North Stars- Winning (Austin), Truthseeking (me), and Flow (Timothy), but I think the actual theme might be “what is an acceptable amount of risk taking?” We eventually got into a discussion of Sam Bankman-Fried, where Austin very bravely shared his position that SBF has been unwisely demonized and should be “freed and put back to work”. He by no means convinced me or Timothy of this, but I deeply appreciate the chance for a public debate.
Episode:
Transcript (this time with filler words removed by AI)
Editing policy: we allow guests (and hosts) to redact things they said, on the theory that this is no worse than not saying them in the first place. We aspire but don’t guarantee to note serious redactions in the recording. I also edit for interest and time.
The perfect exercise doesn’t exist. The good-enough exercise is anything you do regularly without injuring yourself. But maybe you want more than good enough. One place you could look for insight is studies on how 20 college sophomores responded to a particular 4 week exercise program, but you will be looking for a long time. What you really need are metrics that help you fine tune your own exercise program.
VO2max (a measure of how hard you are capable of performing cardio) is a promising metric for fine tuning your workout plan. It is meaningful (1 additional point in VO2max, which is 20 to 35% of a standard deviation in the unathletic, is correlated with 10% lower annual all-cause mortality), responsive (studies find exercise newbies can see gains in 6 weeks), and easy to approximate (using two numbers from your fitbit).
In this post I’m going to cover the basics of VO2max, why I estimate such a high return to improvements, and what kind of exercise can raise it the fastest.
What is VO2max?
A person’s VO₂ max is the maximum volume of oxygen they can consume in one minute. Higher VO2max lets you cardio more intensely, and is correlated with better health and longer lifespan (we’ll quantify this later). This is 100% of what you need to know, the rest is thrown in for fun.
VO2max is measured in ml O2/kg bodyweight/minute. It is sometimes given in Metabolic Equivalents (METs). 1 MET = 3.5ml O2/kg of bodyweight/minute. This is approximately your metabolic expenditure while sitting still.
What physically causes increase in VO2max? It’s a mix of many factors:
Strengthened heart allows you to pump blood faster
Improved lung capacity, which breaks down to
Expansion of the chest cavity, in part due to strengthening of the diaphragm and rib muscles.
Recruitment of new alveoli (the features in your lungs that exchange carbon dioxide and oxygen)
The catch: that meta-analysis averaged together results from multiple studies of very different durations. “That’s okay, they could correct for that, at least crudely” you might be saying to yourself, in which case, congratulations on being better at meta-analysis than these authors, who AFAICT dumped every study into a bag and shook it.
More realistic, yet more shocking headline: an increase of 1 point in VO2max is correlated with 10% lower annual all-cause mortality.
This is based on the largest study in the meta-analysis, Kokkinos et al. Important facts from this study include:
In male veterans, going from low fitness to moderate fitness (defined below) lowered risk of dying by 40%. This was shockingly consistent across age groups, and whether you considered a 5 year or 10 year period. Getting to a high fitness level dropped their mortality rate by another 30%.
I too am wondering why the % change in risk of death doesn’t get larger when you consider a longer period of time.
The middle (“threshold”) range for 4 age categories were 8 to 9, 7 to 8, 6 to 7, and 5 to 6 METs for <50, 50 to 59, 60 to 69, and ≥70 years, respectively. Another source gives average MET for those categories (substituting 40-50 for <50 and 70-80 for >70) as 10, 8.6, 7.3, and 6.1, so the threshold starts 1-2 points lower than average and they converge by your 70s.
Low fitness is the range between the floor of the threshold, and 2 METs lower than that, moderate fitness is the ceiling of the threshold plus 2 METs. If distribution within buckets were uniform, we could treat moving from low fitness to moderate fitness as an increase of 2 METs. If you assume a normal distribution centered around the threshold, it’s somewhat smaller than that.I went with the latter assumption, but not very rigorously.
Caveats
VO2max is measured per kg of total body weight, not lean weight. That means that if you lost 10% of your bodyweight via liposuction but otherwise stayed exactly the same, your VO2max would rise by 1/0.9. This makes VO2max a partial proxy for weight. However the relationship between weight and health, and weight and exercise, is much more complicated than is typically acknowledged.
VO2 is also a proxy for exercise. Right now we don’t have enough information to say that increased VO2, or increased aveoli surfactant, increases lifespan or is merely downstream of exercise that does some other helpful thing.
I’m going to ignore both of these for now, but when you’re doing your own math you should not add effects from potential weight loss, because that might be double counting.
Exercise science sucks. Lifespan is affected by 1000 different factors, none of which scientists can properly control. Lots of researchers have their bottom line already written.
While we’re at it, I should note that I haven’t done deep investigations on any other metrics. Very early in the process I considered others, and VO2max won due to a combination of being promising and easy to measure at home. I don’t have the information to say if VO2max is more or less accurate than other metrics.
How can I measure my VO2Max?
(note: this section is based primarily off of Client’s research, not mine)
The official way involves a mask and measuring equipment and 20 minutes of excruciatingly intense exercise. This is technically the most accurate, but only if it’s set up properly, and is expensive. If you’d like to trade accuracy for ease, use this formula
VO2max ≈ (HRmax/HRrest) ∗ magic_constant
If you would like to get a number without understanding it, you can enter your heart rate in this spreadsheet. If you would like to learn about the magic constant, I’ve defined the terms below.
HRRest is your lowest heart rate when measured first thing in the morning, or ask your friendly neighborhood wearable.
HRMax is your heart rate after exercising at ever increasing intensity until you cannot stand it. If you don’t know this, you can use 208 − 0.7 ∗ age. However if you do so you’ll miss any gains that come from increasing your maximum heart rate, which I’d expect to be at least half.
This definition is circular, because MET hours is a function of hours exercised * exertion level. A decent level of physical fitness will burn 10 MET per hour of very intense exercise.
You may be tempted to use wearable-calculated VO2Max. This is a bad idea because your device has no way to separately track how hard you are working from how hard your heart is beating (Apple Watch attempts this, but simplifies things by assuming all exercise is running on a flat surface).
What are you aiming for? Here is a convenient chart (source). This is measured in ml/kg/min, not METs.
How can I raise my VO2Max?
The best exercise is still the one you do consistently without injuring yourself. Optimization within that is for people who have many choices they enjoy, or who don’t enjoy any but can nonetheless force themselves to work out reliably.
The next best exercises appear to be rich people sports (lifespan wise, you’re better off being an amateur raquetballer than an olympic marathoner, despite racquetball’s barely-above-average VO2max). I didn’t find numbers for polo players but I assume they’re stunning. We’re going to ignore these findings even though the papers claim to have controlled for income.
After that, you have two choices: high intensity interval training (HIIT), and using cross country skiing as your regular mode of transportation.
Why those two? No one has proven an answer, but my wild ass speculation is that you raise VO2max by proving to your body that your existing VO2max is insufficient. You do this by operating at capacity. Since it’s impossible to operate at peak capacity for very long, this can be done in the form of interval training, or by working at near-peak capacity for so long that it uses up your reserves. Or so I surmise.
Back to the literature: within interval training, the number one most important property is still that you do it at all, followed by how much you do it, with one possible cheat. According to this meta-analysis even short interval, low volume, low calendar-time was beneficial, but in order to beat moderate-intensity exercise you need to work a little harder: intervals of >2 minutes, total time of >15 minutes, and at least 4 weeks (number of times per week was not specified, but in other papers it was 2-3).
What’s the cheat? Repeated Sprint Training (RST), in which you go absolutely balls out for 10 seconds and then take a nice 2-4 minute gentle stroll. I love RST because there’s a little bit of lag between working very hard and being miserable, and that lag is longer than the interval. By the time the misery catches up with me I’ve already stopped trying. So I’d really like to believe this, but ShortIT (10-30 second intervals) scored poorly relative to longer intervals, so there’s either some sort of horseshoe effect or the success of RST is a mirage.
Here is the full chart from that paper, which is beautiful except for its absolutely incomprehensible labels. Translations below.
Within Training Periods (how many weeks people exercised according to the plan), the options are short (<= 4 weeks), medium, and long term (>=12 weeks).
Within Session Volume, the options are low (<=4 cumulative minutes under load), medium, and high (>=16 minutes of work). Please join me in a moment of annoyance that L sometimes mean smallest and sometimes biggest.
Within Work Intervals (duration of a single intense bout), the options are short, medium, long, very very short (SIT) (10-30s) and itty bitty (RST) (10s).
MICT stands for “moderate intensity cardio training”, aka non-HIIT exercise. CON stands for control. The longer you go (in calendar time) the less of an advantage HIIT has over MICT, which suggests they are both approaching the same asymptote, HIIT just gets there faster.
SMD stands for “standard mean difference”, which is the difference of the means of the treatment and control groups, divided by the standard deviation. The size of SMD differs between the treatment groups, but you can round it to 3 ml O2/kg body weight/person.
What if I already exercise?
In one study, even Olympic athletes were able to raise VO2max via HIIT training (albeit slower than couch potatoes). If you’re not specifically targeting peak capacity, you can probably improve it. However I believe this asymptotes, so if you’re already doing HIIT in particular there may not be much gains left on the table. The client who commissioned this research was a hard-core pilates practitioner and he did not find HIIT to increase his VO2.
Next Steps
Iamnotadoctor, nor do I hold any other relevant qualifications. But if you’re full of inspiration to follow up on this, here is my suggested plan:
Estimate your VO2Max as described above, or use the spreadsheet.
Identify a form of exercise that is highly accessible to you, that can be done safely at very high intensity.
The more of your body it uses the better, but prioritize lowering obstacles. if your office only has an exercise bike that’s better than needing to travel to an elliptical, even though the elliptical uses your arms and the bike doesn’t.
If you’re new to exercise, spend a few sessions playing around on your activity of choice, to get a sense of where your limits are.
If you believe the research on RST (10 seconds of peak exertion followed by 3 minutes of barely moving. If your environment is cold enough you shouldn’t even sweat), do that.
If you don’t believe the research on RST, gradually increase your time under intensity until you reach 4 non-continuous minutes under intense load.
If your intense intervals are longer than 2 minutes they’re probably not actually peak intensity, so you should have at least 2.
Especially at first, aim for sustainability rather than peak achievement. If going 20% slower is the difference between quitting or sticking through it, slower is obviously the correct choice. You can build up over time.
After 6 weeks, estimate VO2max again. The meta-analysis described above suggests you can expect at least 1 MET (3.5 ml O2/kg body weight/min) over 6 weeks.
Thanks to anonymous client and my Patreon patrons for supporting this post.
Last year Timothy Telleen-Lawton and I recorded a podcast episode talking about why I quit Effective Altruism and thought he should too. This week we have a new episode, talking about what he sees in Effective Altruism and the start of a road map for rescuing it.
I’m going through another health valley, but over on LessWrong I hired DirectedEvolution to investigate the benefits of Xofluza, an anti-flu treatment. His conclusion is that it’s far more effective than Tamiflu, but you can read the whole post and play around with the model to come to your own conclusions.
I’ve previously written about Luck Based Medicine: the idea that, having exhausted all the reasonable cures for some issue, you are better off just trying shit rather than trying to reason more cures into existence. I share LBM success stories primarily as propaganda for the concept: the chance any one cure works for anyone else is <10% (sometimes much less), but a culture where people try things and share their results.
I’ve also previously written about my Very Unlucky Winter. My mattress developed mold, and in the course of three months I had four distinct respiratory infections, to devastating effect. A year later I am still working my way through side effects like asthma and foot pain.
But, uh, I also appear to have cured my hypothyroidism, and the best hypothesis as to why is all the povidone iodine I gargled for all those respiratory infections illnesses.
Usually when I discuss fringe medicine I like to say “anything with a real effect can hurt you”, because it’s a nice catchall for potential danger. In this case, I can be more direct: anything that cures hypothyroidism has a risk of causing hyperthyroidism. The symptoms for this start with “very annoying” and end at “permanent disability or death”, so if you’re going to try iodine, it absolutely needs to be under medical supervision with regular testing.
All that said…
I was first diagnosed with hypothyroidism 15 years ago, and 10 years ago tried titrating off medication but was forced back on. My thyroid numbers were in the range where mainstream MDs would think about treating and every ND, NP, or integrative MD would treat immediately.
Low iodine can contribute to hypothyroidism, and my serum iodine tested at low normal for years, so we had of course tried supplementing iodine via pills, repeatedly, to no result. No change in thyroid and no change in serum iodine levels.
In January of the Very Unlucky Winter, I caught covid. I take covid hard under the best of circumstances and was still suffering aftereffects from RSV the previous month, so I was quite scared. Reddit suggested gargling povidone iodine and after irresponsibly little research, I tried it. My irresponsibility paid off in that the covid case was short and didn’t reach my lungs. I stopped taking iodine when I recovered but between all the illnesses, potential illnesses, and prophylactic use I ened up using it for quite a long period.
My memories of this time are very fuzzy and there were a lot of things going on, but the important bits are: I developed terrible insomnia, hand tremors, and temperature regulation issues. These had multiple potential explanations, but one of them was hyperthyroidism so my doctor had me tested. Sure enough, I had healed my thyroid to the point my once-necessary medication was giving me hyperthyroidism.
Over the next few months I continued gargling with iodine and titrating my medication down. After ~6 months I was off it entirely. I’ve since been retested twice (6 weeks and 20 weeks after ceasing medication) and it looks like I’m clean.
Could this have been caused by something besides iodine? I suppose, and I was on a fantastic number of pills, but I can’t figure out what else it could be. Hypothyroidism has a very short list of curable underlying causes, and none of them are treated by anything I was taking.
So why did gargling iodine work when pills didn’t? It could be the formulation, but given my digestive system’s deepseated issues, I’m suspicious that the key was letting the iodine be absorbed through the mucous membrane of the throat, rather than attempting to through the gut. If that’s true, maybe I can work around my other unresponsive vitamin deficiencies by using sublingual multivitamins. I started them in June and am waiting to take the relevant test.
Thank you to my Patreon patrons for their support of this work.
There is a $500 bounty for reporting errors that cause me to change my beliefs, and an at-my-discretion bounty for smaller errors.
Over the past year I’ve investigated potential interventions against respiratory illnesses. Previous results include “Enovid nasal spray is promising but understudied”, “Povidone iodine is promising but understudied” and “Humming will solve all your problemsno wait it’s useless”. Two of the iodine papers showed salt water doing as well or almost as well as iodine. I assume salt water has lower side effects, so that seemed like a promising thing to check. I still believe that, but that’s about all I believe, because papers studying gargling salt water (without nasal irrigation) are few and far between.
I ended up finding only one new paper I thought valuable that wasn’t already included in my original review of iodine, and it focused on tap water, not salt water. It found a 30% drop in illness when gargling increased in frequency from 1 time per day to 3.6 times, which is fantastic. But having so few relevant papers with such small sample sizes has a little alarm going off in my head screaming publication BIAS publication BIAS. So this is going in the books as another intervention that is promising but understudied, with no larger conclusions drawn.
Note that despite the title, they only gave mouthwashes to participants with symptoms.
This study had 40 participants collect saliva, rinse their mouth with one of four mouthwashes, and then collect more saliva 15 and 45 minutes later . Researchers then compared compared the viral load in the initial collection with the viral load 15 and 45 minutes later. The overall effect was very strong: 3 of the washes had a 90% total reduction in viral load, and the loser of the bunch (chlorhexidine) still had a 70% reduction (error bars fairly large). So taken at face value, salt water was at least as good as the antiseptic washes.
(Normal saline is 0.9% salt by weight, or roughly 0.1 teaspoons salt per 4 tablespoons water)
[ETA 11/19: an earlier version of this post incorrectly stated 1 teaspon per 4 tablespoons. Thank you anonymous]
This graph is a little confusing: both the blue and green bars represent a reduction in viral load relative to the initial collection. Taken at face value, this means chlorhexidine lost ground between minutes 15 and 45, peroxide and saline did all their work in 15 minutes, and iodine took longer to reach its full effect. However, all had a fairly large effect.
My guess is this is an overestimate of the true impact, because I expect an oral rinse to have a greater effect on virons in saliva than in cells (where the cell membrane protects them from many dangers). Saline may also inflate its impact by breaking down dead RNA that was detectable via PCR but never dangerous.
This study had a fairly similar experimental set up to the previous: 12 people per group tried one of three mouth washes, or a lozenge. Participants collected saliva samples immediately before and after the treatments, and researchers compared (a proxy for) viral loads between them.
Well, kind of. The previous study calculated the actual viral load and compared before and after. This study calculated the number of PCR cycles they needed to run before reaching detectable levels of covid in the sample. This value is known as cycle threshold, or Ct. It is negatively correlated with viral load (a smaller load means you need more cycles before it becomes detectable), but the relationship is not straightforward. It depends on the specific virus, the machine set up, and the existing cycle count. So you can count on a higher Ct count representing an improvement, but a change of 4 is not necessarily twice as good as a change of 2, and a change from 30->35 is not necessarily the same as a change from 20->25. The graph below doesn’t preclude them doing that, but doesn’t prove they did so either. My statistician (hi Dad) says they confirmed a normal distribution of differences in means before the analysis, which is somewhat comforting.
This study found a significant effect for iodine and chlorhexidine lozenges, but not saline or chlorhexidine mouthwash. This could be accurate, an anomaly from a small sample size, or an artifact of the saline group having a higher starting Ct value (=lower viral load) to start from.
This study started with 387 healthy volunteers and instructed them to gargle tap (not salt) water or iodine at least three times a day (the control and iodine group also gargled water once per day). For 60 days volunteers recorded a daily symptom diary. This set up is almost everything I could ask for: it looked at real illness over time rather than a short term proxy like viral load, and adherence was excellent. Unfortunately, the design were some flaws.
Most notably, the study functionally only counted someone as sick if they had both nose and throat symptoms (technically other symptoms counted, but in practice these were rare). For a while I was convinced this was disqualifying, because water gargling could treat the pain of a sore throat without reducing viral load. However the iodine group was gargling as often as the frequent watergarglers, without their success. Iodine does irritate the throat, but gargling iodine 3 times per day produced about as much illness as water once per day. It seems very unlikely that iodine’s antiviral and throat-irritant properties would exactly cancel out.
Taking the results at face value, iodine 3x/day + water 1x/day was no better than water 1x/day on its own. Water 3.6x/day led to a 30% reduction in illness (implicitly defined as lacking throat symptoms)
The paper speculates that iodine failed because it harmed the microbiome of the throat, causing short term benefits but long term costs. I liked this explanation because I hypothesized that problem in my previous post. Alas, it doesn’t match the data. If iodine traded a short term benefit for long term cost, you’d expect illness to be suppressed at first and catch up later. This is the opposite of what you see in the graph for iodine. However it’s not a bad description of what we see for frequent water gargling – at 15 days, 10% more of the low-frequency water garglers have gotten sick. At 50 days it’s 20% more – fully double the proportion of sick people in the frequent water gargler group. For between 50 and 60 days, the control group stays almost flat, and the frequent water garglers have gone up 10 percentage points.
What does this mean? Could be noise, could be gargling altering the microbiome or irritating the throat, could be that the control group ran out of people to get sick. Or perhaps some secret fourth thing.
None of the differences in symptoms-once-ill were significant to p<0.05, possibly as a result of their poor definition of illness, or the fact that the symptom assessment was made a full 7 days after symptom onset.
Assuming arguendo that gargling water works, why? There’s an unlikely but interesting idea in another paper from the same authors, based on the same data. They point to a third paper that demonstrated dust mite proteins worsen colds and flus, and suggest that gargling helps by removing those dust mite proteins. Alas, their explanation of why this would help for colds but not flus makes absolutely no goddamn sense, which makes it hard to trust an already shaky idea.
A boring but more reasonable explanation is that Japanese tapwater contains chlorine, and this acts as a disinfectant.
Dishonorable Mention: Vitamin D3 and gargling for the prevention of upper respiratory tract infections: a randomized controlled trial
I silently discarded several papers I read for this project but this one was so bad I needed to name and shame.
The study used a 2×2 analysis examining vitamin D and gargling with tap water. However it was “definitively” underpowered to detect interactions, so they combined the gargling with and without vitamin D vs. no gargling with and without D into groups, without looking for any interaction between vitamin D and gargling. This design is bad and they should feel bad.
Conclusion
Water (salted or no) seems at least as promising an antiviral as other liquids you could gargle, with a lower risk of side effects. So if you’re going to gargle, it seems like water is the best choice. However I still have concerns about the effect of longterm gargling on the microbiome, so I am restricting myself to high risk situations or known illness. However the data is sparse, and ignoring all of this is a pretty solid move.
Thank you to Lightspeed Grants and my Patreon patrons for their support of this work. Thanks to Craig Van Nostrand for statistical consults.
There is a $500 bounty for reporting errors that cause me to change my beliefs, and an at-my-discretion bounty for smaller errors.
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Aceso Under Glass 
