Can you please share some evidence (peer-reviewed scientific research publications / clinical data) supporting this? Curious about the potential mechanisms.
Inflammation is typically experienced when the body is responding to an infection or injury. It is a normal, and as per current understanding, a necessary part of the body's immune response.
The Cleveland clinic has a nice, informative page if you want more information [0]
[edited to add]
The response of the innate immune system to the infectious agent / injury is what causes inflammation - i.e., for instance, fever, swelling, etc. It is a very very complex multi-cascade process, but one of the first responses to an injury, for instance, is the release of signalling molecules that results in localised swelling, slightly elevated temperature (which makes the tissue a little more inhospitable to bacteria / viruses), etc. all of which serve as the front line defense. <This is a severe over-simplification> Wikipedia has a good explanation that goes into the roles and triggers of the inflammatory response. [1]
Acute inflammation in response to infections and injuries is a good thing, and from everything we know, it is a necessary part of the immune response. The challenge is when the same inflammation response is mis-directed to target the body - for instance, in rheumatoid arthritis, and other inflammation related auto-immune disorders.
The latest Kurzgesagd video on exercise seemed to imply that (excepting sudden changes in activity level) caloric burn rate is constant regardless of lifestyle, but if you are sedentary, the "excess" calories are burned "unproductively" (e.g. increased inflammation).
So this seems to imply excess calories are a cause of chronic inflammation.
Also, the ketogenic diet has been shown to significantly reduce inflammation, though I'm not sure if that's from reducing carbs, or reducing something else associated with high carb intake.
> caloric burn rate is constant regardless of lifestyle
This is obviously false as stated, extreme athletes consume vastly more calories than sedentary people of their same weight. Phelps was rather famous for a 10,000+ calorie per day diet but even just manual labors need significantly more calories.
I’m assuming there’s some unspecified criteria such as while sleeping?
It's just plain not true. Claims like this coming out in the past few years are based on Herman Pontzer's research in which he measured activity levels and energy expenditure among the Hadza, a forager group in Africa, testing the hypothesis that they'd be using a lot more energy because of how active they are. He found their energy expenditure on average wasn't actually much different than the average for sedentary Americans and developed something called the constrained energy expenditure model. This just postulates that the human body has various ways of compensating in the long term for high activity levels. If less energy is available for basic life processes that are not critical to immediate survival, those process will be modulated downward. Importantly, one of these is inflammation, which is likely why exercise reduces inflammation. At the very extreme end of this, you see things like Marshall Ulrich when he was attempting to break the record for time running across the continental United States seeing things like his hair and nails stopped growing. Female endurance athletes commonly stop having periods. Male endurance athletes often have reduced testosterone production.
But this compensation is nowhere near 100% and it also isn't clear to what extent this is mediated by food availability and possibly the intensity of the activity. The Hadza don't have a lot of food and they're spending all day walking around. Similar studies have been conducted on the Amish, who are doing far harder manual farm labor and have enormous amounts of food, and these studies found much high energy expenditure among the Amish compared to post-industrial sedentary Americans, as well as an average 9% bodyfat for males for whatever that is worth. Similarly, the experiences of endurance athletes with bad health symptoms like amenorrhea and low bone mineral density are limited to people who feel pressure to be as small as possible and don't eat anywhere near enough food. Those who simply eat more don't have the same experiences.
As you stated, we also have quite a bit of clear cut existence proofs that energy expenditure is not simply constant among all people regardless of activity. Pontzer himself has studied some of these extremes to figure out how much energy a human actually can expend. From what I recall, it seemed to be around 3.5 times whatever your base metabolic rate is, at least in the long run. Over short bursts, energy expenditure can be up to 10 times base. The greatest longer duration energy demands he has seen in the field is the Tour de France for men and pregnancy for women, both of which are about equal and seem to represent the limits of what humans can do. Obviously, the people doing these things are eating far more than they would be if they weren't doing those things. Nutrition advice for athletes is nearly the opposite of what it is for the obese and sedentary. Eat sugar like there's no tomorrow. Get as many liquid calories as possible. Avoid high fiber because it'll sit in your gut forever slowing down all other digestion and making you uncomfortable. There's a reason for this.
Two of my favorite podcasts, Stronger by Science and Iron Culture, was in the former case and is in the latter hosted by one of the researchers who works in Herman Pontzer's lab, and he is constantly expressing frustration over how the findings and model get misrepresented by the time they telephone down to pop science communicators and diet influencers. The model simply says that expending X calories per day in exercise will not result in a net difference of X calories expended in total. It'll be some percentage less than 100. But it won't be 0%. Exercise and activity don't make no difference at all.
I'd never heard of this Kurzgesagt thing, but it appears to be a group of animators that make cartoon explainer videos of basically everything? That might be entertaining but is probably not the best way to learn about the frontiers of contemporary nutrition and exercise science.
Glucose and fructose will react non-specifically with proteins in the body, particularly when present in excess. These non-specific reactions are recognized as foreign and/or defective, which triggers inflammation. The apply named RAGE protein is one mediator of this response (https://en.wikipedia.org/wiki/RAGE_(receptor)).
HbA1C results from the non-enzymatic reaction between glucose and hemoglobin. It serves as a measure of your long-term glucose level and is elevated in diabetics.
Low carb diets dramatically reduce this source of inflammation.
That's missing the point. If this technique can result in longer lives for people with both good diets and not, it is a genuinely novel innovation in human life span that can't be replaced with better diet alone.
It could well be that this protein is good for you when you’re young but not that good for you when you are older.
For example, young people might encounter more new infection sources, and thus need a faster/stronger responding immune system. This protein might be evolved for giving you that, with a side effect of having too strong an immune system at older age.
Evolution may not yet have found a solution that turns down its production at later age, or it might have evolved it at some time, but found its benefits do not outweigh the cost of maintaining the necessary control mechanism.
It’s far from a given that having more humans live to old age has evolutionary benefits.
What happens when you eliminate the "good inflammation" in those with bad diets? Then what? There's likely going to be unintended consequences, naturally. My point, eliminating one symptom usually means eventually creating another.
It's not missing the point. The point is that a lot of people live with chronic inflammation caused by poor lifestyle choices and that results in many diseases later in life, including Alzheimer's.
The point is that chronic inflammation is bad. The comment I'm replying to isn't recognizing that it's just saying "oh inflammation is fine because it's a response to injury" which is very much missing the point.
How much of the consequences of a poor life style can be mitigated by simply reducing the chronic inflammation response by the body?
I'd love it if cheap shitty food wasn't bad for me. At the end of the day a calorie is a calorie and many animals handle the stuff that shortens our life with no problem.
Look at it another way, if dogs can't eat chocolate but humans can, is the problem with chocolate or with dogs?
A calorie is certainly not just a calorie. Different foods are metabolized differently and affect the body in different ways, regardless of otherwise equal caloric values. Take fructose, glucose, and ethanol as an example.
The problem there is with dogs, and has nothing to do with calories. Dogs (and many other animals) are simply not able to tolerate chocolate like humans can. Conversely, humans can't tolerate eating rancid meat and cat poop, but dogs can eat those things easily and not get sick. Lots of substances are poisonous to certain species, and non-poisonous to other species.
Also, the reason chocolate is unhealthy isn't because of the cacao plant, it's because of all the added sugar used to make it taste good, since raw cacao (or cocoa, which you get after cooking it) is horribly bitter.
Chronic inflammation is bad. Is chronic inflammation always caused by auto-immune?
Or is it also caused by things like pollutants, poor diet, or other "first world" problems?
I ask because I used to be very concerned with particulate matter (I still am, but I used to too), and it seemed a big problem with that was it triggering inflammation.
It's been a while since I looked into this, but diet is a major factor with inflammation. Sugars, seed oils and grain-fed dairy. (Also if you eat the grains yourself!) Keto lowers it, caloric restriction lowers it (conversely excess calories coupled with sedentary lifestyle increase it), intermittent fasting lowers it.
I forget about exercise, I think it's a case of temporarily increasing it (hours) and then lowering it long-term.
Speaking from personal experience diet plays as much a role as medication in decreasing inflammation. Sugars, gluten, and some* nuts and seeds are indeed pro-inflammatory (many seeds and nuts are anti-inflammatory)
I don't think there's a pattern suggesting that. Many autoimmune diseases are more prevalent in less polluted parts of the world. The strongest links appear to be genetic, in that some diseases (e.g., Sjogren's syndrome) are clearly more common in people of certain geographic descents.
There is no distinction regardless of cause, imo. Stress can epigenetically cause an autoimmune disease, and so can pollution (including smoking), excessive alcohol, processed food diet, sedentariness, etc. Often it is a number of factors that can lead to a chronically overactive immune response.
I am the founder of an industrial edtech company, with some prior experience in the K12 space.
Your analysis of the market structure and the challenges is consistent with my experience - I'd like to add 2 points though:
1. Building on what you've said about VC-level returns, while edtech (and industrial edtech) may not necessarily be fields where VC funded unicorns can actually form and then survive to profitability, I believe there is sufficient need and space for companies that are investable and can grow into profits / valuations in the 10s /100s of millions - they can follow the startup format, etc.; just not VC investable, as you've noted.
2. In the space of skill development (i.e., adults / professional learning), I would like to add that for many skills, as industries get more sophisticated (I am taking of manufacturing, automotive, energy, oil & gas, infrastructure, petrochemicals, infrastructure), there is value for the company in upskilling their staff - simply because that does directly convert to profitability if done well; and at least puts a floor on issues that poor or absent training may cause - like safety, quality, etc. So even if it is a cost, it is a cost that can directly affect their topline / bottomline, and I believe there is an opportunity here.
I think bootstrapped with a small team of under 10 people, Karpathy can get to revenue of $20M just from the developer market. That's a pretty great outcome if VCs aren't involved.
The submission was flagged, and I am not sure I understand why since the only (negatively) critical discussion I see is on the ambiguity over the title in the HN submission; flagging a submission appears to take it off the HN homepage, and I feel a title ambiguity in the face of the significance of the submission itself isn’t a strong reason for removing the submission from HN? :)
There are (at the time of posting this comment) no comments raising any substantive issue with the arxiv submission itself (which ofc has to go through the peer review process of publication, and hopefully the original authors will respond / rebut this new article) - so curious why its been flagged? It’s not dead, so cannot vouch for it.
If folks in the HN community who have flagged it have done so because there are serious issues with what the paper is asserting, please comment / critique instead of just flagging it. If it’s because of the ambiguity in the title, I hope @dang and the moderators editorialize - there are some valuable comments in this thread that helped me understand what the issue is and what the bug is!
and there are some anatomical differences between mice and humans..
So its open at this point whether it is relevant directly to humans.
IIRC, mice do not get Alzheimer’s, for instance. There are mouse models (genetically engineered)that exhibit some of the physiological symptoms of Alzheimer’s; but mice make particularly poor models for human neurology [1]- so this reach for using these essentially biomechanical structures to identify parallels and try to target a cure for neuro-degerative disorders in humans: seems more like a grant application attempt. I do wish press releases were a little more circumspect about such claims.
They do say they plan to verify findings in primates as well so perhaps the accomplishment here is more concerning the methodology. So there me be some greater merit to this work going forward.
I think it would be more interesting for this kind of study to verify these measures that can only be obtained in animals with neuroimaging. There have been some interesting attempts to move monitor aspects of CSF flow through MRI but we need to make sure we are measuring what we think we are before using in the clinic
I tried your platform for some experiments using an arduino and it was a breeze, and an absolute treat to work with.
The platform documentation and support is excellent.
Thank you for developing it and offering it, along with documentation, to enable folks like me (who are not coders, but understand some coding) to test and explore :)
This is amazing to hear! Good luck with any other project you're gonna build next!
I can recommend checking out building for more different hardware targets - there is a lot of interesting chips that can take advantage of Edge ML and are awesome to work with
Gesture recognition using the onboard gyroscope and accelerometer (I think - it was 2 years ago!), and it took me some part of an afternoon.
I also used these two resources (the book was definitely useful; less sure if the arduino link the the same one I referred to then), which I found to be useful:
Some questions, if you are still around to answer, because this is exciting!
1) Have you read about Vannevar Bush, and what he has written, and his body of work?! :)
2) What sort of people are you looking for / to work with?
3) Would it need to be full-time? Are you looking to hire people full time (the generalists you mention), or are you comfortable working with people who are happy not cashing a cheque from you because they have jobs and other commitments / priorities, but still believe in what you are building and would like to invest significant time in supporting / driving the mission forward for some limited (or no) financial compensation?
Because I’d like to check if I fit! :)
(I’ve also spammed you on twitter with a dm, but with more personal details, etc.)
Yes I'm reasonably familiar with Vannevar Bush's amazing body of work. We're likely to hire passionate and interesting outsiders on the whole, but really anyone who is extremely curious, pragmatic, and happy to get their hands dirty on everything from the lowest levels of implementation detail on up could be a good fit.
It's easiest to work with people full-time, but I wouldn't set any hard and fast rules.
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On Friday, Judge Donato vowed to investigate Google for intentionally and systematically suppressing evidence, calling the company’s conduct “a frontal assault on the fair administration of justice.” We were there in the courtroom for his explanation.
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Perhaps because the peer-reviewed paper was published only recently (23rd Nov) - while not a perfect system (see the recent issues with the retraction of the super-conductivity paper by Nature), I think it not a bad thing that journalists are covering such reports once they have undergone the peer-review process - however flawed it may be, and not just based on the university or research group published press-release announcing the results before the peer-review process is complete.
Also, while the final result can be simply stated in a headline, performing the analysis that rules out all known sources of error is very, very difficult and can take years to validate.
At some level, I think this is orthogonal to technological progress.
One possible way of getting at this is to ask if people were more ‘happy’ when there wasn’t this level of tech available - and I’m not sure the answer is yes - I mean, there’s the mythos of ‘a simple life’ and ‘noble savages’, but from what I’ve read of life even a 100 years back - I would surmise folks were as unhappy / miserable then too - but likely for different reasons.
I think expecting just tech to make us happy is framing the wrong problem space.
Maybe happy isn’t the right word, but I think it’s pretty clear people were more content and felt a sense of purpose. Social media has made things worse, but it’s really the loss of community and religion that has led to the crisis of loneliness and depression among todays people.
Modern loneliness is a far more multifaceted issue than it’s often presented as.
For instance I’m sure that a major factor is the need for people to move great distances away from family and the community they grew up in to be able to find education, living wages, and other forms of opportunity. That breaks existing connections and makes it harder to form new ones, but I never see that talked about.
Those kinds of movements aren't new though: Entire generations in many a country ended up emigrating across the sea, back when it was far slower and dangerous, to make their fortunes, as their home was too poor to handle more than one son. And today we have our home culture on our phones. I can watch TV from my home country, and my home team's soccer matches live. I can video call whenever, for free.
So maintain connection has never been easier, and migration is not any worse. I have no doubt there are far more things than social media making people more unhappy than historically, but having to move away from where we were born isn't it.
Moving itself is probably wouldn’t be so bad if it weren’t as frequent, for instance if maybe moving once after college would be it for most people. That’d still give people time to set down roots.
Instead it’s often necessary to move repeatedly, for reasons varying from going to school to getting a job to finding housing with room for kids to just trying to keep rent from eating up the majority of one’s paycheck.
In my case I’ve moved 9 times in the ~15 years since I turned 20 and it’s very likely I’ll be moving again in the future. It’s been very disruptive for maintaining connections, even with the power of modern communications at my disposal. I’ve more or less grown used to it and am kind of introverted anyway so I’m not depressed but I could see where others might not be so lucky.
As opposed to living with a spouse that abused them/who they were not in love with, without a way to divorce. Or a huge percentage of people having to experience losing their children?
It was simply not spoken about, people either poisoned their husband if it got that bad, or lived a sad life in silence.
