doingtheiroming

The fact of its complexity is why we need to start treating it as a unit. Reductive thinking, research and treatment won't lead us to a proper understanding of it. Among the potential benefits of the development of AI is hopefully an improvemnt in our ability to reason about and understand complex entities like the immune system. I think it's more likely that a new specialism will develop from that, that doctors developing one from what exists today.

I'm sure you're awayre that lots of evidence now that MS and many other AI diseases are caused / induced by acute or chronic viral infections:

https://med.stanford.edu/news/all-news/2022/01/epstein-barr-...

It really feels at this point that not by connecting these diseases together and treating them as a class, we're missing the woods for the trees. Sadly, all of the economic incentives are to keep treating them separately and reductively because chronic diseases are great long-term revenue generators. TBC, I'm not attacking the drug companies here (UC was a killer until pred was discovered in the 1950s and Vedolizumab is working fantasically well for me) but we need the immune system to be treated as genuine clinical and research discipline to really cure these things.

My last UC flare was preceeded by a bout of shingles which is caused by an opportunistic latent virus. My doctors always talk of my immune system as being over-active. It really seems to me that it's more the immune system becoming disordered - which latent viruses play a major role in. My docs aren't remotely interested in having that discussion because it doesn't involve the details of gut epithelial cells. Fascinating as they are, I don't think we're going to cure UC or any other AI disease by focusing on them.

I've never seen a rhematologist. It does feel like the specialism that's closest to immunology. My docs always ask about joint pain and there's certainly overlap between arthritis and other inflammatory diseases like UC. My grandmother had terrible arthritis and as it tends to be more common in women, it seems likely that's the reason rheumatology in general is overlooked and understaffed. Biologics like Infliximab started out as arthritis treatements and were re-purposed as IBD treatmetns (generally more useful for UC than Crohns).

A friend who was recently diagnosed with UC (but with many other obviously AI symptoms / conditions) has managed to get himself referred to a Rheumatologist which is almost certainly a good thing.

But regardless of how good a rheumatologist might be at dealing with it, it isn't a fix for the issue that the immune system isn't treated as a first class citizen in medicine.

Neuropathy is not a serious issue for me, but like depression, eczema and the rest it's something that I get as either as a co-symptom in a flare or a signal that a flare is coming. The docs like to use c-reactive protein as a biomarker, but I tend to find it's a trailing indicator of problems. I start expecting a flare when the subsidiary symptoms appear (eczema etc.) as they tend to be leading indicators. The problem is that because my GIs are only really interested in GI symptoms, they see those things as unrelated until the GI symptoms appear.

Other folk I know with AI diseases have seen similar patterns and have for example seen improvements to things like PN when they went on anti-inflammatory drugs (5-ASA in the case of one friend) which were prescribed for UC.

I don't think the PN was caused by the Azathioprine. I have always felt it was a co-sypmption that I get as a "bonus" when the colitis flares.

The book that accompanies the Kurzgesacht series is very good. I bought it for my eldest who enjoyed it enormously. He's been complaining about his HS biology lessons being rubbish as a result.

This is straightforward protection for Air France and the other big airlines. Cheap flights are used to make sure that seats are filled. Minimum pricing will mean more planes will fly with empty seats and therefore less efficiently. There will be fewer flights, but the ones that remain will be more expensive and more polluting on a per-seat basis. The wealthy will continue to pay and enjoy less crowded planes. Bonus!

Yet another case of the environmental Baptists providing cover for the polluting bootleggers.

Auto Immune Disorder (IBD in my case) sufferer here. I sometimes wonder why we're all not more annoyed that we get sent to specialists for the parts of our body (GI in my case) where the immune system is causing most damage at a given moment who will ask questions about other symptoms that we now have a good idea are likely the result of the same inflammation (depression, joint pain, peripheral neuropathy, CFS, etc. etc. etc.) but at no point, is there a department of immunology that takes over or even contributes.

I've worked my way through azathioprine (poisons your bone marrow to reduce white blood cell count - great for getting skin cancer) to vedolizumab which targets a single gut immune system signaling molecule. I'm lucky in that both have induced full remission which means all the inflammation related symptoms go away, not just the colitis. But I know many people who aren't that lucky and who get some symptoms controlled while others continue unabated. And then there are folk like you who seem to get nothing.

The immune system in complex in the proper sense but we still treat the problems it causes reductively. Worse, most of the research that is done treats it reductively also. If COVID had a silver lining it was that it seemed immune system research got a couple of decades of research done in two years. But when I'm talking to my GI, I really feel that nothing has changed and that at some point, I'm going to flare again, get deeply depressed, be unable to move properly or exercise, lose feeling in my toes and after the steroids have ruined me a bit more, I'll be stuck on a new IBD drug and will hope for the best.

We need these diseases to be treated systemically, as a class and for the immune system to have it's own specialists in research and treatment. They would be able to act as sherpas for sufferers but more importantly, would be a point of nucleation for new ideas about the immune system since they would be exposed to the gamut of problems sufferers face.

It makes me angry, which is probably a flare-risk factor...

The ONS, like Eurostat is a genuinely useful organization full of people who care about the accuracy of numbers. When the original data was released, they were clear that there were likely to be revisions. As it turns out the revisions are bigger than expected but the justification that during the Corona crisis, businesses didn't prioritize the form filling required by the ONS, is reasonable. There is also a change in methodology for many of the global stats agency in how GDP is calculated. The ONS is actually ahead of the game in getting that implemented. It's also had a positive effect, one that is likely to be replicated in other countries as they adopt the changes.

Mainframe will be with us for a long time yet. The reasons are many and complex.

Lack of impetus

There are plenty of neobanks out there that have built scalable, secure infrastructures using modern development practices in the cloud. But despite growing rapidly, none of them has the scale to challenge the big banks. Similarly in areas like the airline industry, the big airlines are all old and back-end technology is rarely the deciding factor in whether or not one airline is more efficient than another. There simply isn't as strong an impetus to change as you'd expect.

Risk

There is very little incentive for any given executive at one of these firms to take the risk involved in staking their reputation on a big technology migration. Equally, there's nothing quite like a failed transformation project to destroy the careers of those associated with it. If you think mainframe is antediluvian, take a look at the ERP software the same companies are running. Layer upon layer of legacy with custom code built to manage myriad edge-cases that nobody understands anymore. Why take the risk when you can build a new system that integrates with the mainframe using (for example) a modern database that gives you a modern transactional API while micro-batching updates back to the mainframe. The incentives are all to create additional cruft.

Outsourcing

Most if not all of the big banks, airlines etc. have outsourced considerable parts of their operations over the years. In doing so, institutional knowledge was shifted out of the business into those outsourcers. The outsourcers in turn have little incentive to drive transformation of the mainframe given that a move to cloud sees their revenue deriving from the infrastructure management go to near zero. The outsourcers don't even have to act in bad faith for this to be a major problem. McKinsey and the rest thrive on complexity and by advising clients to outsource, they layered organizational and contractual complexity on the technology complexity, making the problem of transformation increasingly irreducible.

After risk, outsourcing is probably the most important factor since it is extremely difficult to create outsourced structures which maintain and develop an organic link between those responsible for business processes, and those responsible for technology. The result is an ever growing pile of sclerotic processes, dysfunctional governance bodies and uni-functional teams (often themselves outsourced to different parties for competitive purposes) that purport to control but which really just create complexity.

Outsourcing has served to worsen the organizational complexity that most mainframe users already suffered from. The result is a situation in which any programme of work to get off mainframe becomes fearsomely complex. I've worked in places which would have regular meetings of large parts of the company to try to coordinate major business process change in a single area. I've seen companies nearly break themselves trying to bring a single outsourced business function back in house. The question is why, when they're so incredibly inefficient and inflexible, they aren't competed away. That's a different question on which I have my own opinions, but this comment is too long already.

Knowledge

The loss of COBOL and other mainframe technology knowledge is real. I remember working at a bank in the EU around 2010 where I sat with a bunch of elderly gentlemen (walking sticks were a theme) who had been contracted back into the bank to develop integration between an ancient mainframe application and something modern the bank was building.

But that stereotype aside (there are surprising numbers of younger mainframe experts in India thanks to outsourcing), the problem is real, particularly when it comes to migration of software from mainframe to cloud using modern development practices. Any migration away from mainframe software requires understanding the whole technology stack and more importantly, how that stack interacts with the equally complex stack of business processes.

AI code interpretation and generation might take a COBOL program and translate it into modern code, or even help re-architect it using modern principles. But without that understanding of the business processes as well as the up and downstream dependencies in their many forms, anything other than piecemeal change looks terrifying to anyone who might try to move away from mainframe.

IBM

The fact is that mainframe is an effective technology stack. But more importantly, IBM has become extremely good at both keeping it up to date while also owning the best ways of modernizing it.

They're good at making sure they control the path away from mainframe. The best, simplest and lowest risk approaches to getting off legacy code on mainframe are either developed by or bought by IBM. By enabling Linux on mainframe and providing straightforward migration paths from legacy code to that platform, IBM (and its many partners) ensures that modernization of mainframe for the most part means staying on mainframe. This has gone through multiple phases and taken lots of forms over the years but really, IBM has done a stupendous job of ensuing that the future of mainframe is usually mainframe.

The advent of AI code interpretation and generation is another example of this. IBM has already announced their own AI tooling to help customers make the migration to mainframe Linux faster and smoother: https://newsroom.ibm.com/2023-08-22-IBM-Unveils-watsonx-Gene....

The challenge for any AI startup or professional services company wanting to help customers move away from mainframe is that the people best placed to sell those tools are... IBM and its partners.

Might the situation change?

AI code interpretation and generation is getting better all the time. LLM context sizes are growing rapidly. The possibility of fine-tuning a code-generation model using a business' own source code is there. It's even possible that businesses who no longer have source code can use AI to analyze and decompose binaries. The days when AI can analyze a whole software infrastructure, re-architect it and re-write it whole-cloth are coming. But even with those tools, the organizational layering, process cruft and generalized loss of institutional knowledge is going to make elimination of mainframe a long-term, high-risk project.

This is not to say that it won't happen. But technology change can only ever happen successfully at the rate an organization is able to change along with it. The organizations which still use mainframe tend to be the biggest, most complex and sclerotic organizations on the planet. IBM is going to be enjoying the benefits of what it built decades ago for decades to come.

It’s worth reading about refineries and chemical plants. We’ve all heard of Bhopal and other disasters but it’s worth bearing in mind just how few disasters happen in these fearsomely complex and dangerous plants. Almost all are managed successfully by the private sector.

There was an interview with Jim Radcliffe recently in which he described Ineos’ approach to safety. It’s a variation on what’s described my Steven J. Spears in his case study of Alcoa. The truth is that the private sector has innovated much of what’s best in modern safety practice in a way that has made monumentally dangerous industrial processes routine.

There are perhaps good reasons to keep nuclear weapons management in the public sector. Canards about the safety record of the private sector are not though.

There’s plenty of skepticism. It’s the zero-cost position here. But there are good and bad skeptical positions. The good one involves people attempting to replicate and publishing results whether positive, negative or somewhere in between. The bad one consists of sitting in forums and threads being, “the voice of reason”.

If there’s a real problem, it’s that we have still not made publication of negative results sufficiently attractive. That’s still a problem throughout science and one we desperately need to address since it is what would let us think more clearly in situations like this.

The positive view here is that we are 5-10 years from being able to search for materials computationally using AI. That would potentially be more valuable than a single RTS.

Worth noting that because the man pages are so good, GPT4 is a rather good OpenBSD sysadmin. If you get stuck on anything these days, you can ask it.

I do 30 mins to an hour of a language every day. After I’m done in Duolingo I work my way through a news story on a local news aggregator (I.e. dumbed down) website using Google Translate to figure out things I don’t understand by picking out words. I find trying to identify phrases in the articles useful as it’s starting to give me a sense of basic idiom.

Feels like a good way to consolidate and push forward. It also gives me a bit of culture since news articles are revealing of the way people think.

This means that most European banks, big companies and government departments will soon be fined by the EU... The following could be said of almost all large corporations and institutions, including the year long project that failed to catalog data sources effectively:

"When ordered to produce information about what 149 different data systems within Meta do, and what parts of Meta’s business use them, the company was unable to respond. This was despite having conducted a year-long investigation of those systems."

There is no point having a law which essentially no company can be compliant with. It means that the law will almost certainly be applied only by exception and hence capriciously. The likes of Facebook may be able to use that as a defense despite their breaches being egregious.

As a side-note, the idea that Meta only has 149 in-scope data systems sounds ridiculous.

The assumption that things like this necessarily increase support for republicanism is probably misplaced. In Italy and Greece Governments have been effectively overthrown by the EU (or ECB/IMF) in fairly open ways with technocrats put in charge. In both countries support for the EU is running at very high levels despite that. Higher levels in fact that when it happened.

The U.K. monarchy clearly lacks the wherewithal to influence Australian politics today that it possibly had back then and has nothing like the influence (through the Euro) of the ECB on the democratic Governments of Eurozone countries.

The lesson might actually be (ironically if so) that the monarchy would be more resilient to republican opinion if it wielded more power. It is the perceived pointlessness of it that will lead to its decline, not any strength.

I’m just finishing up reading Dominic Sandbrook’s, “Adventures in Time:Alexander the Great” with my 12 year old. Great fun and an incredible tour. Once we’ve done, we are going to watch the “Trial of Alexander the Great”. I know the verdict but I won’t add a spoiler:

https://classicsforall.org.uk/news-and-events/events/moot-tr...

Windows NT layered IO drivers were a PitA. Because those higher in the stack would have to deal with whatever alterations those lower had made to the IO stream, device driver writers would try to force their driver to load as low as possible to avoid writing all the code to handle it.

File system filter drivers were where the chaos this caused manifested. If there was just one loaded, you might not see any problems (though the anti-virus guys could be relied on to find a way...). But once you had a few (AV, file system quotas, backup etc.) all sorts of horrible things would start happening.

People always complained about blue screens but experience taught us to love and cherish them as it meant the damage a filter driver had done had actually been caught rather than it silently doing horrible things to files. The other nice thing about the BSODs was that you could always pinpoint the driver that had pooped its pants by analyzing the dump file.

In the NT4 days, manipulating the load order was a simple registry entry for the driver. We put a lot of time and effort into finagling them to figure out which were the worst offenders. In the end, we just figured out which combinations of filters were worst and quit using them.

Windows 2000 (I think) fixed this by removing the ability of drivers to manipulate the load order. That forced the driver writers to up their game a bit and write the code necessary to deal with whatever something lower in the stack had done.

This is getting traction because the London media class has noticed people taking the mickey out of their adoption of the vocal fry from their New York brethren. They don't want regionals laughing at them.

It's vitally important that Southerners keep talking in silly accents. It's useful to spot people who are going to try to steal your stuff using emails.

The both sound middle class.

It’s wonderful. I love the word “slurring” for sliding. It describes the way a cart might move through mud perfectly.

After all the stories about neobanks getting into trouble for not doing money laundering checks effectively, it's nice to see one being smart about it.

Probably because it’s so disappointed at how Scientific American has declined.

Some years ago…

Monks: opinion that requires authority

One of the challenges faced in the early days was simply to get the bacteria to reproduce. It’s not clear for any given bacteria what substrate and food source is useful. Not being able to do that was an obstacle to the analytics since much of the basic data couldn’t be developed. It seems we are better at that now.

I can't. But there's good evidence that inflammation is linked with depression and steroids unquestionably reduce inflammation. They may well have further effects. They are certainly not something I want to take consistently.

Cursive is still taught with ferocity in Dutch primary schools. When done well it's pretty, enables rapid writing and note taking, and at least part of learning to write that way is to learn how to read it. Since everyone older than you will still write that way, it's useful to be able to read it.

It's likely the inflammation that's causing the depression rather than any particular molecule produced by a bacterium though. I have the same experience with UC to the extent that taking steroids causes almost immediate relief of the depressive symptoms and I relapse when I taper. In my last flare, I tried to track depressive symptoms against CRP levels in my blood but being depressed, lost interest... Joking aside, I also wasn't getting the blood tests with sufficient frequency for it to be useful. "The Inflamed Mind" by Edward Bullamore is a good read on the subject.

I find it odd that people acknowledge the fearsome complexity of the gut biome with one breath before saying that they hope to isolate a single molecule made by it to positively affect another complex phenomenon, with the next.

The same promise was held out for Ulcerative Colitis / Crohns. Composition of the gut biome clearly plays a role in both illnesses. But the search for small molecule drugs building on this observation seems to have been fruitless. That might be because it's not the presence of a particular molecule in bacterial poop that's influencing the disease but something about the biome as a whole. More positively, it might also be that the tools available at the start of that search were nothing like as good as those we have now as interest in the brain / biome link grows. I tend to think it unlikely that small molecules for effective treatment of anything much will result from this but I've no doubt a great deal of useful and important things will be learned in the process. I'd love to be wrong.